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MOD Exam 1 > Genetic Disorders > Flashcards

Genetic Disorders Flashcards

1
Q

What is the most life-threatening feature of Marfan syndrome

A

Cardiovascular lesions including mitral valve prolapse, AAA

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2
Q

Carrier males of fragile X syndrome pass the trait through their phenotypically normal daughters to affected grandchildren, thus these males are

A

Normal transmitting males

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3
Q

Pseudohermaphrodite

A

disagreement between phenotype and gonadal sex

i.e. female with ovaries but external male genitalia

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4
Q

Fragile X tremor/ataxia differs from fragile X syndrome how?

A

Fragile X tremor/ataxia results from a toxic gain of function mutation in the FMR1 gene

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5
Q

What is a distinguishable feature of trinucleotide-repeat mutations?

A

They are dynamic, i.e. the degree of amplification increases during gametogenesis

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6
Q

Cause of Prader-Willi Syndrome?

A

Deletion in the paternally derived chromosome 15

15, del(15)(q11.2q13)

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7
Q

Clinical features of velocardiofacial syndrome?

A

facial dysmorphism

cleft palate

cardiovascular abnl

learning disabilities

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8
Q

What is the idea behind pharmacogenetics?

A

Enzyme deficiencies are unmasked after exposure to a drug

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9
Q

What is the most common structural abnormality in females with Turner Syndrome?

A

Production of a partial monosomy of the X chromosome

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10
Q

what is the most commonly used stain for a karyotype?

A

Giemsa stain

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11
Q

What are the common congenital heart defects a patient with trisomy 21 may have?

A

Defects of the endocardial cushion: ostium primum, ASD, AV valve malformation, VSD

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12
Q

Autosomal dominant disorders are manifested in the heterozygous state, what does the imply?

A

At least one parent is usually affected and each child has a 50% chance of have the disease

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13
Q

Blood group Ags are an example of codominance, what does this mean?

A

Both of the alleles contribute to the phenotype

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14
Q

Ring chromosome and its consequences

A

Results from a break at both ends of the chromosome with the fusion of the damaged ends

These chromosomes do not behave properly in mitosis or meiosis and have serious consequences

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15
Q

Phenylketonuria (PKU) is an AR disorder with a deficiency in what enzyme?

A

phenylalanine hydroxylase (PAH)

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16
Q

Hurler syndrome, MPS I, is characterized by

A

Hepatosplenomegaly by 6-24 mo

Growth retardation, coarse facial features, skeletal abnl, corneal clouding

Death by 6-10 y/o 2/2 cardiovascular complications including coronary artery deposits

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17
Q

Heteroplasmy

A

tissues and individuals harbor both WT and mutant mtDNA

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18
Q

Morphologic changes seen in MPS

A

Mucopolysaccharide accumulation in mononuclear phagocytic cells, endothelial cells, smooth M. cells, fibroblasts

Cells are distended with clear cytoplasm

Swollen lysosomes with periodic acid-schiff-positive material inside

Zebra bodies

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19
Q

What is a common clinical manifestation of kyphoscoliosis EDS?

A

Ocular fragility with rupture of cornea and retinal detachment

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20
Q

What is the common outcome of AD disorders?

A

Reduced gene product

Dysfunctional or inactive protein production

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21
Q

MPS is characterized by

A

Coarse facial features

clouding of the cornea

joint stiffness

mental retardation

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22
Q

What is the term for a single gene mutation that leads to many end effects?

A

Pleiotropism

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23
Q

What is the common COD in patients with Marfan syndrome?

A

Aortic dissection

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24
Q

What traits do AR disorders have that distinguish them from AD disorders?

A

expression is usually more uniform

Complete penetrance is common

onset frequently early in life

Many mutations involve enzymes

Parents are unaffected carriers

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25
Q

Trinucleotide-repeat mutations involve amplification of a sequence of 3 nucleotides, what nucleotides are commonly involved?

A

Cytosine (C)

Guanine (G)

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26
Q

Of the types of Gaucher disease, what type is the most common?

What are the manifestations

A

Type I

Accumulation of glucocerebroside in phagocytes without CNS involvement

Marked by splenic and skeletal involvement

Pancytopenia and thrombocytopenia 2/2 splenomegaly

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27
Q

β-thalassemia results from what type of mutation?

A

Nonsense mutation

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28
Q

Robertsonian translocation and its consequences

A

A translocation between two acrocentric chromosomes; leads to one very large chromosome and one extremely small chromosome

Small chromosome is lost but person with normal phenotype

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29
Q

Lyon Hypothesis (lyonization)

A

In females, one X chromosome is randomly inactivated during development

It can be from eiher the mother or the father

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30
Q

What percentage of down syndrome patients are a result of mosaicism?

A

1%

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31
Q

What is the most common form of Niemann-Pick disease?

A

Type C

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32
Q

Mechanism behind Familial hypercholesterolemia

A

decreased synthesis or decreased function of LDL receptors leading to a defective transport of LDL into the cells and an increase in cholesterol in the blood

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33
Q

What dominates the clinical picture of Von Gierke disease (and other hepatic type glycogenoses)

A

Hepatomegaly and hypoglycemia

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34
Q

Common lysosomal storage diseases

A

Tay-Sachs disease

Gaucher disease

Neimann-pick diease (A and B)

MPS I (Hurler)

MPS II (Hunter)

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35
Q

What is the immediate and major source of plasma LDL, the circulating form of cholesterol?

A

IDL (intermediate density lipoprotein)

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36
Q

What are the common disorders associated with defects in receptors and transport mechanisms?

A

Familial hypercholesterolemia

CF

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37
Q

Tx for Gaucher disease

A

Allogeneic hematopoietic stem cell transplant

Recombinant enzyme replacement

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38
Q

A range of severity of a disease suggests it is what type of disorder?

A

Multigenic

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39
Q

What is a morphologic hallmark seen in diseases caused by trinucleotide repeat mutations?

A

Accumulation of aggregated mutant proteins in large intranuclear inclusions

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40
Q

Where is the mutation that leads to Marfan syndrome?

A

the FBN1 (fibrillin-1 gene) on chromosome 15q21.1

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41
Q

what explains the unusual inheritance pattern of fragile X syndrome?

A

during the process of oogenesis, but not spermatogenesis, premutations can be converted into mutations by triplet-repeat amplification

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42
Q

What is the inheritance pattern of Marfan Syndrome

A

Autosomal dominant, usually 2/2 missense mutation

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43
Q

A new mutation arises, resulting in a child developing a disease, is a parent typically affected by the disease as well?

A

No

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44
Q

New mutations that arise in AD disorders seem to occur in?

A

Germ cells of relatively old fathers

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45
Q

Fragile X syndrome affects what gender more?

What do these affected individuals usually have?

A

Males

Mental retardation, with an IQ between 20 and 60

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46
Q

The exit of cholesterol from the lysosomes requires what two proteins?

A

NPC1 and NPC2

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47
Q

Chromosomal translocation

A

A segment of one chromosome is transferred to another

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48
Q

Gene mutated in classic type EDS

A

COL5A1 and COL5A2

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49
Q

Where is the mutation that causes fragile X syndrome?

A

Familial mental retardation-1 gene (FMR1) on chromosome Xq27.3

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50
Q

What is a common clinical manifestation is vascular EDS

A

rupture of the colon and large aa

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51
Q

What is one of the most frequent Mendelian disorders?

A

Familial hypercholesterolemia

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52
Q

If an AR mutation is of low frequency in a population, what is likely the cause?

A

Consanguineous marriage

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53
Q

Tay-Sachs disease results from what type of mutation?

A

A frameshift mutation with base insertion

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54
Q

What type of mutation leads to Tay-Sachs

A

base insertion leading to frameshift mutation

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55
Q

Gene mutated in vascular EDS

A

COL3A1

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56
Q

Mosaic turner syndrome patients have a 45,X cell population along with what other cell types?

A

Either normal or abnormal cell types

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57
Q

An error in meiosis or mitosis leading to a cell without an exact multiple of 23 is referred to as

A

Aneuploid

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58
Q

Cause of complex multigenic disorders

A

interactions between multiple variant forms of genes and environmental factors

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59
Q

McArdle disease is classified as a myopathic form of glycogen storage disease, what enzyme is deficient in this disease?

A

Muscle phosphorylase

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60
Q

Anaphase lag usually results in monosomy, why?

A

During anaphase, one of the homologous chromsomes in meiosis or one of the chromatids in mitosis lags behind and is left out of the cell nucleus, resulting in one normal cell and one monosomic cell

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61
Q

3 categories of human genetic disorders

A

Single gene mutations (Mendelian)

Chromosomal

Complex multigenic

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62
Q

Why is Chr 22q11.2 deletion syndrome often missed?

A

D/t the variable clinical features including:

congenital heart defects

abnl of palate

facial dysmorphism

developmental delay

variable degrees of T-cell immunodeficiency

Hypocalcemia

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63
Q

What enzyme is deficient in Hunter syndrome (MPS II)

A

L-iduronosulfate sulfatase

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64
Q

Where is the mutation that causes Huntington disease?

What kind of mutation is this?

A

HTT gene on chromosome 4p16.3

Gain-of-function mutation

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65
Q

What enzyme is deficient in Hurler syndrome (MPS I)

A

α-L-Idouronidase

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66
Q

What are the two main patterns of dz associated wtih AD disorders?

A

Regulation of complex metabolic pathways are subject to feedback inhibition

Key structural proteins: collagen, cytoskeletal elements of RBC membrane (spectrin)

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67
Q

Turner syndrome results from what?

A

Complete or partial monosomy of the X chromosome

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68
Q

What are clinical features associated with Fragile X syndrome?

A

long face with a large mandible

Large everted ears

large testicles

hyperextensible joints

high arched palat

Mitral valve prolapse

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69
Q

Common clinical manifestations of MPS

A

Hepatosplenomegaly

Skeletal Deformities

Valvular lesions

SUbenothelial arterial deposits (coronary aa)

Brain lesions

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70
Q

Variable expressivity

A

Traits are expressed differently in individuals with the mutation

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71
Q

What trinucleotide repeat is involved in Fragile X syndrome?

A

CGG

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72
Q

What differentiates Trisomy 18 (Edwards syndrome) and Trisomy 13 (Platau syndrome) from trisomy 21?

A

Malformations are more severe and wide ranging, infants rarely survive past the first year

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73
Q

Why is there no y-linked inheritance in males with an x-linked disorder?

A

Males are typically infertile

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74
Q

What features are common to all sex chromosome disorders?

A

They are subtle, chronic problems relating to sexual development and fertility

Many are first recognized at puberty

The greater the number of X chromosomes, the greater the likelihood of mental retardation

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75
Q

Where does imprinting typically occur?

A

in the ovum or the sperm, depending

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76
Q

Common indications to test for genetic diseases in older patients

A

Inherited CA syndromes

Atypically mild monogeneic disease (attenuated CF)

Neurodegenerative disorders

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77
Q

What population is commonly seen to have PKU?

A

scandinavians

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78
Q

Huntington diesease is characterized by what clinical manifestations?

A

Progressive movement disorders and dementia 2/2 degeneration of striatal GABAergic neurons

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79
Q

What tissues are commonly involved in EDS?

A

Skin, ligaments and joints d/t being rich in collagen

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80
Q

Clinical features of Prader-Willi syndrome

A

Mental retardation

Short stature

Hypotonia

Profound hyperphagia

Obesity

Hypogonadism

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81
Q

What differentiaties Hunter syndrome from the other forms of MPS?

A

It is of x-linked inheritance

Does not involve clouding of the cornea

Expresses milder clinical course

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82
Q

What has a strong influence on the incidence of trisomy 21?

A

Maternal age

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83
Q

What are the clinical features associated with McArdles disease?

A

Painful muscle cramps after exercise

Exercise fails to raise blood lactate levels d/t defect in glycolysis

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84
Q

Mutations involving single genes follow one of three patterns of inheritance, what are they?

A

Autosomal dominant

Autosomal recessive

X-linked

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85
Q

loss of function mutations arise from what type of mutation?

What does this mutation result in?

A

An autosomal dominant mutation

Results in the loss of activity of the gene product

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86
Q

How does mosaicism arise?

A

Mitotic errors that occur early in development give rise to two or more populations of cells with different chromosomal complement in the same individual

Commonly occurs in sex chromosomes

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87
Q

All mucopolysaccharidoses are inherited through autosomal recessive pattern except which form?

A

MPS II (Hunter)

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88
Q

Causative mutations involving the expansion of trinucleotide repeats usually involve what nucleotides?

A

Cytosine (C)

Guanine (G)

89
Q

Manifestation of chromosomal disorders?

A

Arise from structural or numerical alteration in the autosomes and sex chromosomes

90
Q

Tx for PKU

A

Dietary retrictions, reducing phenylalanine intake

(artificial sweetners often with phenylalanine)

91
Q

What clinical features are common to most types of females with Turner syndrome

A

Coarctation of the aorta

Short stature

Amenorrhea

Cubitus valgus

Webbing of the neck

Fibrotic (streak) ovaries

92
Q

Functional differences between a paternal allele and a maternal allele arise from?

A

Genomic imprinting

93
Q

What is the COD of infants and young children with trisomy 21?

A

Cardiac conditions

94
Q

What is a known enzyme deficiency that is unmasked after taking a specific drug?

A

Glucose 6-phosphate dehydrogenase leads to severe hemolytic anemia after taking the antimalaria drug Primaquine

95
Q

Anticipation is seen in fragile X syndrome, what does this mean?

A

Clinical features of fragile X syndrome worsen with each successive generation

96
Q

Clinical manifestations of PKU

A

phenylalanemia which leads to mental retardation, hypopigmentation of skin and hair, eczema

97
Q

What is the most common chromosomal disorder?

A

Down syndrome (trisomy 21)

98
Q

Gaucher Disease is caused by a deficiency in what enzyme?

What does it lead to?

A

Glucocerebrosidase

Accumulation of glucocerebroside in phagocytes, with subsequent activation leading to the release of pro-inflammatory cytokines (IL-1, TNF, IL-6)

99
Q

Gene mutation for Kyphoscoliosis type EDS

A

Lysyl hydroxylase

100
Q

Characteristics of complex multigenic disorders

Provide examples

A

Common (polymorphisms)

Low penetrance

Ex: Atherosclerosis, DM, HTN, autoimmune dz, height and weight

101
Q

Characteristics of chromosomal disorders

A

Uncommon

High penetrance

102
Q

Of the types of Gaucher disease, what form is the most aggressive?

What are the manifestations

A

Type II

Progressive CNS involvement, hepatosplenomegaly, early death

103
Q

What is the most common lysosomal storage disorder?

A

Gaucher disease

104
Q

What sex chromosome disorder is the most common cause of male infertility?

A

Klinefelter Syndrome (47, XXY)

105
Q

Regardless of the number of X chromosomes, the presence of a Y chromosome determines the sex of the person to be?

A

Male

106
Q

Secondary accumulation

A

Results from impaired autophagy, leading to the accumulation of dysfunctional mitochondria

107
Q

Tay-Sachs disease results from a mutation where?

What does this lead to?

A

α-subunit locus on chromosome 15

severe deficiency of hexosaminidase A resulting in the inability to metabolize GM2 gangliosides (accumulates in neurons, retina, heart, liver and spleen)

108
Q

What type of mutation gives rise to CA and some congenital malformations?

A

Somatic cell mutations

109
Q

What are the clinical manifestations of EDS?

A

Skin is hyperextensible

Joints are hypermobile

Skin is fragile and vulnerable to trauma (gaping injuries difficult to repair d/t lack of normal strength)

Diaphragmatic hernia

110
Q

What is the most distinctive feature in individuals with fragile X syndrome?

A

macro-orchidism (large testicles)

Observed in 90% of affected prepubertal males

111
Q

Euploid

A

Any exact multiple of haploid number of chromosomes (23)

112
Q

Mitochondrial disorder inheritance pattern

A

All affected mothers pass the disease onto all children

Affected males do not pass on the trait

113
Q

The resolution of banding in a karyotype is markedly improved if the cells are obtained in what phase of the cell cycle?

A

Prophase

114
Q

What are the clinical features of a patient with down syndrome?

A

flat facial profile

oblique palpebral fissures, epicanthic folds

Wide gap between great toe and second toe

Single palmar crease

Fissured tongue

Small hypoplastic ears

Mental retardation

Congenital heart disease

115
Q

What are the mechanisms for which loss of fibrillin in Marfan syndrome leads to the clinical manifestations?

A

loss of structural suppport in microfibril rich CT

Excessive activation of TGF-β signaling

116
Q

What type of mutation gives rise to inherited diseases?

A

Germ cell mutations

117
Q

True hermaphrodite

A

contains both ovarian and testicular tissue

118
Q

What pattern of inheritance does CF follow?

A

Autosomal recessive

119
Q

If an insertion or deletion does not occur in multiples of 3, what happens when the gene is transcribed and translated?

A

There is a frameshift mutation which typically involves addition of incorrect AA followed by a premature stop codon (truncation)

120
Q

What is the mode of inheritance of EDS?

A

Encompasses all three modes (AD, AR, x-linked)

121
Q

Predominant population affected by Neimann-Pick dz?

A

Ashkenazi jews

122
Q

Cause of death in patients with MPS?

A

MI
Cardiac decompensation

123
Q

Cause of Angelman syndrome?

A

deletion of maternally derived chromosome 15

15, del(15)(q11.2q13)

124
Q

57% of females with turner syndrome are missing an entire chromosome, what karyotype is this?

A

45, XO

125
Q

Morphologic changes seen with Gaucher disease

A

Distended phagocytes (gaucher cells) in liver, spleen, bone marrow, lymph nodes, tonsils, thymus

Crumpled tissue paper appearing fibrillary cytoplasm

126
Q

Klinefelter syndrome has what classic karyotype pattern and what genetic defect causes this syndrome?

A

47, XXY

Meiotic nondisjunction

127
Q

Prader-willi syndrome and Angelman syndrome both arise from deletions on what chromosome?

What makes these syndromes different?

A

15q12

Whether it is the paternal or maternal chromosome

128
Q

Consequences of enzymatic mutations

A

accumulation of substrates (galactosemia)

decreased amount of end product (Lesch-nayan sydrome)

failure to inactivate a tissue damaging substrate (α1-antitrypsin def)

129
Q

What percentage of females who are carriers of fragile X syndrome are affected?

A

30-50%

(i.e. show mental retardation)

130
Q

Ectopia lentis is so uncommon, that if found (esp bilat) it should raise suspicion for what disorder?

A

Marfan syndrome

131
Q

What is the single most important cause of primary amenorrhea?

A

Turner Syndrome

132
Q

Clinical features of DiGeorge syndrome

A

thymic hypoplasia with resultant T cell immunodeficiency

Parathyroid hypoplasia leading to hypoparathyroidism + hypocalcemia

Cardiac malformations

Mild facial anomalies

Cleft palate

133
Q

Von Gierke Disease is a hepatic glycogen storage disease characterized by the deficiency of what enzyme?

A

Glucose-6-phosphatase

134
Q

ABO blood type results from what type of mutation?

A

single base deletion

135
Q

involvement of what tissues dominates the clinical picture of tay-sachs disease?

A

Neurons and retina

136
Q

Where is the gene mutation that causes cystic fibrosis?

A

CFTR on chromosome 7q31.2

137
Q

What disease is associated with a deficiency in lysosomal glucosidase (acid maltase)?

A

Pompe dz

138
Q

CF results from what type of mutation?

A

base deletion

139
Q

Categories of mechanisms involved in mendelian disorders

A

Enzyme defects and their consequences

Defects in membrane receptors and transport systems

Alterations in structure, function or quantity of non-enzyme products

Mutations resulting in unusual drug rxns

140
Q

Why is it difficult to distinguish between a mendelian disorder and a multifactorial disease?

A

Variable expressivity and reduced penetrance of a single mutant gene may account for a range of level of diseases, similar to a multifactorial disease

141
Q

Clinical manifestations of tay-sach’s disease

A

Normal at birth

Motor and mental deterioration develops around 6mo, become obtunded, flaccid, blind and demented

Death by 2-3 y/o

Cherry red spot in the macula

142
Q

Isochromosome

A

One arm of a chromosome is lost and the remaining arm is duplicated; results in a chromosome with either two short arms (p) or two long arms (q)

143
Q

Clinical features of Angelman syndrome

A

Mental retardation

Ataxia

Seizures

Inappropriate laughter

“happy puppets”

144
Q

Familial hypercholesterolemia results from a mutation in a receptor, what receptor is this?

A

LDL

145
Q

What is the most severe form of Niemann pick dz and what are the manifestations?

A

Type A

Extensive neuro involvement

Marked accumulation of sphingomyelin viscerally

Cherry red spot in retina

Hepatosplenomegaly

Death by 3 y/o

146
Q

What is the most common sex chromosome abnormality in females?

A

Turner syndrome

147
Q

Missense mutation

A

A single base change that changes the meaning of the sequence of the encoded protein

Ex: Sickle cell anemia CTC to CAC changes glutamine to valine

148
Q

Autosomal recessive disorders are characterized by

A

mutations in both alleles at a given loci

149
Q

Clinical manifestations of Niemann-Pick dz type C

A

Ataxia

Vertical supranuclear gaze palsy

dystonia

dysarthria

psychomotor regression

150
Q

Mucopolysaccharidoses result from mutations which lead to

A

deficient enzymes that degrade glycosaminoglycans, causing a build up of mucopolysaccharides in the ground substance of CT

151
Q

What causes aneuploidy?

A

Nondisjunction

Anaphase lag

152
Q

What trisomies are similar in karyotype and clinical features to trisomy 21?

A

Trisomy 18 and trisomy 13

153
Q

Glycogen storage diseases result in hereditary deficiencies in what types of enzymes?

A

Enzymes responsible for the synthesis or degradation of glycogen

154
Q

Patients with Klinefelter syndrome are at higher risk of developing what other conditions?

A

Breast CA

Type II DM and metabolic syndrome

Mitral valve prolapse

Osteoporosis

Extragonadal cell tumors

Autoimmune dz such as SLE

155
Q

What is distinct about a PKU patients urine and sweat?

A

Musty or mousy odor to it

156
Q

Turner sydrome is characterized by?

A

Hypogonadism in phenotypic females

157
Q

The mutation in the LDL receptor, leading to familial hypercholesterolemia results in what clinical manifestations?

A

Tendinous Xanthomas

Increased cholesterol which leads to premature atherosclerosis and increased risk of MI

158
Q

What is the most common genetic cause of congenital malformations?

A

Multifactorial inheritance

159
Q

What type of mutation leads to Niemann-Pick type A?

A

Missense mutation resulting in complete deficiency of sphingomyelinase

160
Q

Patients with Down syndrome are at a 10-20 fold increased risk at developing what condition?

A

Acute leukemia

161
Q

Patients with CF prone to getting Infections by what organisms?

A
  • Haemophilus Influenzae*
  • Pseudomona aerugionsa*
162
Q

If a patient has an MI at a young age (before 20 y/o), what condition does this raise suspicion for?

A

homozygotic familial hypercholesterolemia

163
Q

How is mitochondrial DNA transmitted?

A

Mothers transmit their mtDNA to all offspring (M and F), fathers DO NOT pass on mtDNA

164
Q

Define mutation

A

a permanent change in the DNA

165
Q

Nondisjunction

A

Occurs during gametogenesis, a gamete has either an extra chromosome or one less chromosome, result in trisomy or monosomy

166
Q

Neimann-Pick Disease (types A and B)

A

Lysosomal accumulation of sphingomyelin d/t deficiency in sphingomyelinase

167
Q

What is the most common form of GM2 gangliosidosis?

A

Tay-Sachs disease

168
Q

How does a robertsonian translocation contribute to Trisomy 21?

A

translocation occurs in which the q arm of chromosome 21 is translocated to another chromosome such that the long arm of chromosome 21 carries all of the functional genes

169
Q

Common test for CF?

A

Sweat chloride

170
Q

Treatment options for lysosomal storage diseases

A

Enzyme replacement therapy

Substrate reduction therapy

Molecular chaperone therapy

171
Q

Velocardiofacial syndrome results from

A

Chr 22q11.2 deletion syndrome

172
Q

Complex disorders result from

A

collective inheritance of many polymorphisms

173
Q

What is the second most common cause of mental retardation after Down Syndrome?

A

Fragile X syndrome

174
Q

What are the characteristics of CF?

A

abnormal function of the epithelial chloride channel protein, resulting in disorderly ion transport affecting fluid secretions

175
Q

Down syndrome is most commonly cause by what genetic problem?

A

Meiotic nondisjunction

176
Q

Morphologic changes seen in Tay-Sachs disease

A

Neurons are dilated with cytoplasmic vacuoles that represent distended lysosomes filled with gangliosides

Whorled lysosomes

177
Q

Ehlers-Danlos Syndrome (EDS) arises from defects in

A

synthesis or structure of fibrillar collagen

178
Q

If an insertion or deletion occurs in multiples of 3, what happens when the gene is transcribed and translated?

A

the reading frame remains intact but an abnormal protein is produced

179
Q

What is the threshold effect?

A

A minimum number of mutatnt mtDNA must be present in a cell or tissue before oxidative dysfunction gives rise to disease

180
Q

What common mucopolysaccharides accumulate in CT?

A

Dermatan sulfate

Heparan sulfate

Keratan sulfate

Chondroitin sulfate

181
Q

Patients with Chr 22q11.2 deletion syndrome are at high risk of developing what condition?

A

Psychiatric disorders including schizophrenia and bipolar disorder

182
Q

Where is the mutation that causes Niemann-pick type C?

A

NPC1 gene responsible for producing NPC1 involved in cholesterol transport from the lysosome

183
Q

When the trinucleotide repeats in the FMR1 gene exceed 230, the gene becomes methylated resulting in its transcriptional suppression and the absence of FRMP, what is the function of this protein?

A

Selectively binds mRNAs associated with polysomes and regulates their intracellular transport to dendrites

Acts as a translation regulator

184
Q

Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial disorder characterized by

A

progressive bilateral loss of central vision

185
Q

How many cases of Trisomy 21 can be attributed to a Robertsonian translocation?

A

~4%

186
Q

Characteristics of mendelian disorders?

A

alterations in a single gene leading to abnormal product or a decrease in the amount of normal product produced

187
Q

Why is mtDNA of maternal inheritance?

A

the ova contain numerous mitochondria while spermatozoa contain few, if any, mitochondria

188
Q

Clinical features of Klinefelter Syndrome (47, XXY)

A

Eunuchoid body habitus with abnormally long legs

Small testes and small penis

lack of male secondary sex characteristics (deep voice, facial hair)

Gynecomastia

189
Q

What morphologic changes are seen in pompe disease?

A

Cardiomegaly leads to cardiorespiratory failure and death within 2 yrs

Hepatomegaly (mild)

190
Q

What type of mutation leads to cystic fibrosis?

A

3 base deletion

191
Q

Primary accumulation

A

deficiency in lysosomal enzyme renders a substrate incompletely catabolized, leading to the accumulation of the metabolite within the lysosome

192
Q

Paternal imprinting results in?

A

Paternal allele being inactivated (silenced)

193
Q

Indications for prenatal testing of fetuses at risk for cytogenetic abnormality

A

Advanced maternal age

Parent known to carry a balanced chromosomal rearrangment

Fetal anomalies observed on US

Routine maternal blood screening indicating an increased risk of Trisomy 21 or other trisomies

194
Q

What trinucleotide repeat is seen with huntington disease?

A

CAG

195
Q
A
196
Q

What is the most important cauese of increased mortality in children with turner syndrome?

A

Cardiovascular abnormalities

(typically left sided)

197
Q

Characteristics of a mendelian disorder?

A

Rare

Highly penetrant

Ex: sickle cell anemia

198
Q

In what population is Tay-sachs disease common?

A

Eastern european populations

Ashkenazi Jews

199
Q

Sex-linked disorders follow what pattern of inheritance?

A

x-linked

often recessive

200
Q

Incomplete penetrance

A

Individual has the mutation but has a normal phenotype

201
Q

Mutations in promotor or enhancer sequences leads is a noncoding mutation which results in what?

A

Inability of the transcription factors to bind leading to decreased transcription and translation

202
Q

The most severely affected infants with Turner syndrome present with what clincial features?

A

Swelling of the feet and hands

Cystic hygroma that eventually subsides, leaving bilateral neck webbing

203
Q

What is the most common autosomal recessive form of EDS?

A

Kyphoscoliosis type

204
Q

What are the 3 subgroups of glyocgen storage diseases?

A

Hepatic type

Myopathic type

Miscellaneous (aspects of both above)

205
Q

Anticipation

A

A genetic disorder is passed onto the next generation, the symptoms become apparent at an earlier age with each generation; also associated with an increase in severity of sxs as it is passed on

Ex: Huntington dz, myotonic dystrophy

206
Q

What disease is caused by trinucleotide repeats occurring during spermatogenesis?

A

Huntington disease

207
Q

What is the most common lethal genetic disease that affects caucasian populations?

A

Cystic Fibrosis

208
Q

Categories of single gene disorders with nonclassical inheritance patterns

A

Diseases caused by trinucleotide repeats

Disorders caused by mutations in mitochondrial genes

disorders associated with genomic imprinting

Disorders associated with gonadal mosaicism

209
Q

When is a gene termed polymorphic?

A

When it has two alleles, each of which occurs at a frequency of at least 1% in the population

210
Q

Morphologic changes seen in Niemann-Pick disease

A

Enlarged cells

Foamy cytoplasm

Zebra bodies (lysosomes with concentric lammellations)

Vacuolation of neurons

Some have cherry red spot on retina

211
Q

DiGeorge syndrome results from what?

A

Results from Chr 22q11.2 deletion syndrome

212
Q

Maternal imprinting results in?

A

Transcriptional silencing of the maternal allele

213
Q

Three key mechanisms by which unstable repeats cause disease

A

Loss of function

Toxic gain of function

Toxic gain of function mediated by mRNA

214
Q

Clinical manifestations of Marfan syndrome

A

Tall with long extremities

Double jointed

Frontal bossing

Ectopia lentis

Aortic dissection

215
Q

What disorder is an example of variable expressivity?

A

Neurofibromatosis type 1

216
Q

What are the clinical features associated with cystic fibrosis?

A

Abnormally viscous secretions

chronic lung dz (emphysema and bronchiectasis)

Pancreatic insufficiency

Steatorrhea

Cirrhosis

Meconium ileus

Male infertility

217
Q

What common malformations are considered to be of multifactorial inheritance?

A

Cleft lip and cleft palate

Neural tube defects

218
Q

What two disorders are common in Ashkenazi Jews and also present clinically with cherry red spot in the macula?

A

Tay Sachs disease

Niemann-Pick types A and B

MOD Exam 1 (5 decks)

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