Genetic Disorders Flashcards
1
Q
What is the most life-threatening feature of Marfan syndrome
A
Cardiovascular lesions including mitral valve prolapse, AAA
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
3
Q
Pseudohermaphrodite
A
disagreement between phenotype and gonadal sex
i.e. female with ovaries but external male genitalia
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
5
Q
What is a distinguishable feature of trinucleotide-repeat mutations?
A
They are dynamic, i.e. the degree of amplification increases during gametogenesis
6
Q
Cause of Prader-Willi Syndrome?
A
Deletion in the paternally derived chromosome 15
15, del(15)(q11.2q13)
7
Q
Clinical features of velocardiofacial syndrome?
A
facial dysmorphism
cleft palate
cardiovascular abnl
learning disabilities
8
Q
What is the idea behind pharmacogenetics?
A
Enzyme deficiencies are unmasked after exposure to a drug
9
Q
What is the most common structural abnormality in females with Turner Syndrome?
A
Production of a partial monosomy of the X chromosome
10
Q
what is the most commonly used stain for a karyotype?
A
Giemsa stain
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
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
13
Q
Blood group Ags are an example of codominance, what does this mean?
A
Both of the alleles contribute to the phenotype
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
15
Q
Phenylketonuria (PKU) is an AR disorder with a deficiency in what enzyme?
A
phenylalanine hydroxylase (PAH)
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
17
Q
Heteroplasmy
A
tissues and individuals harbor both WT and mutant mtDNA
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
19
Q
What is a common clinical manifestation of kyphoscoliosis EDS?
A
Ocular fragility with rupture of cornea and retinal detachment
20
Q
What is the common outcome of AD disorders?
A
Reduced gene product
Dysfunctional or inactive protein production
21
Q
MPS is characterized by
A
Coarse facial features
clouding of the cornea
joint stiffness
mental retardation
22
Q
What is the term for a single gene mutation that leads to many end effects?
A
Pleiotropism
23
Q
What is the common COD in patients with Marfan syndrome?
A
Aortic dissection
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
25
Trinucleotide-repeat mutations involve amplification of a sequence of 3 nucleotides, what nucleotides are commonly involved?
Cytosine (C)
Guanine (G)
26
Of the types of Gaucher disease, what type is the most common?
What are the manifestations
Type I
Accumulation of glucocerebroside in phagocytes without CNS involvement
Marked by splenic and skeletal involvement
Pancytopenia and thrombocytopenia 2/2 splenomegaly
27
β-thalassemia results from what type of mutation?
Nonsense mutation
28
Robertsonian translocation and its consequences
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
29
Lyon Hypothesis (lyonization)
In females, one X chromosome is randomly inactivated during development
It can be from eiher the mother or the father
30
What percentage of down syndrome patients are a result of mosaicism?
1%
31
What is the most common form of Niemann-Pick disease?
Type C
32
Mechanism behind Familial hypercholesterolemia
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
33
What dominates the clinical picture of Von Gierke disease (and other hepatic type glycogenoses)
Hepatomegaly and hypoglycemia
34
Common lysosomal storage diseases
Tay-Sachs disease
Gaucher disease
Neimann-pick diease (A and B)
MPS I (Hurler)
MPS II (Hunter)
35
What is the immediate and major source of plasma LDL, the circulating form of cholesterol?
IDL (intermediate density lipoprotein)
36
What are the common disorders associated with defects in receptors and transport mechanisms?
Familial hypercholesterolemia
CF
37
Tx for Gaucher disease
Allogeneic hematopoietic stem cell transplant
Recombinant enzyme replacement
38
A range of severity of a disease suggests it is what type of disorder?
Multigenic
39
What is a morphologic hallmark seen in diseases caused by trinucleotide repeat mutations?
Accumulation of aggregated mutant proteins in large intranuclear inclusions
40
Where is the mutation that leads to Marfan syndrome?
the FBN1 (fibrillin-1 gene) on chromosome 15q21.1
41
what explains the unusual inheritance pattern of fragile X syndrome?
during the process of oogenesis, but not spermatogenesis, premutations can be converted into mutations by triplet-repeat amplification
42
What is the inheritance pattern of Marfan Syndrome
Autosomal dominant, usually 2/2 missense mutation
43
A new mutation arises, resulting in a child developing a disease, is a parent typically affected by the disease as well?
No
44
New mutations that arise in AD disorders seem to occur in?
Germ cells of relatively old fathers
45
Fragile X syndrome affects what gender more?
What do these affected individuals usually have?
Males
Mental retardation, with an IQ between 20 and 60
46
The exit of cholesterol from the lysosomes requires what two proteins?
NPC1 and NPC2
47
Chromosomal translocation
A segment of one chromosome is transferred to another
48
Gene mutated in classic type EDS
COL5A1 and COL5A2
49
Where is the mutation that causes fragile X syndrome?
Familial mental retardation-1 gene (FMR1) on chromosome Xq27.3
50
What is a common clinical manifestation is vascular EDS
rupture of the colon and large aa
51
What is one of the most frequent Mendelian disorders?
Familial hypercholesterolemia
52
If an AR mutation is of low frequency in a population, what is likely the cause?
Consanguineous marriage
53
Tay-Sachs disease results from what type of mutation?
A frameshift mutation with base insertion
54
What type of mutation leads to Tay-Sachs
base insertion leading to frameshift mutation
55
Gene mutated in vascular EDS
COL3A1
56
Mosaic turner syndrome patients have a 45,X cell population along with what other cell types?
Either normal or abnormal cell types
57
An error in meiosis or mitosis leading to a cell without an exact multiple of 23 is referred to as
Aneuploid
58
Cause of complex multigenic disorders
interactions between multiple variant forms of genes and environmental factors
59
McArdle disease is classified as a myopathic form of glycogen storage disease, what enzyme is deficient in this disease?
Muscle phosphorylase
60
Anaphase lag usually results in monosomy, why?
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
61
3 categories of human genetic disorders
Single gene mutations (Mendelian)
Chromosomal
Complex multigenic
62
Why is Chr 22q11.2 deletion syndrome often missed?
D/t the variable clinical features including:
congenital heart defects
abnl of palate
facial dysmorphism
developmental delay
variable degrees of T-cell immunodeficiency
Hypocalcemia
63
What enzyme is deficient in Hunter syndrome (MPS II)
L-iduronosulfate sulfatase
64
Where is the mutation that causes Huntington disease?
What kind of mutation is this?
HTT gene on chromosome 4p16.3
Gain-of-function mutation
65
What enzyme is deficient in Hurler syndrome (MPS I)
α-L-Idouronidase
66
What are the two main patterns of dz associated wtih AD disorders?
Regulation of complex metabolic pathways are subject to feedback inhibition
Key structural proteins: collagen, cytoskeletal elements of RBC membrane (spectrin)
67
Turner syndrome results from what?
Complete or partial monosomy of the X chromosome
68
What are clinical features associated with Fragile X syndrome?
long face with a large mandible
Large everted ears
**large testicles**
hyperextensible joints
high arched palat
Mitral valve prolapse
69
Common clinical manifestations of MPS
Hepatosplenomegaly
Skeletal Deformities
Valvular lesions
SUbenothelial arterial deposits (coronary aa)
Brain lesions
70
Variable expressivity
Traits are expressed differently in individuals with the mutation
71
What trinucleotide repeat is involved in Fragile X syndrome?
CGG
72
What differentiates Trisomy 18 (Edwards syndrome) and Trisomy 13 (Platau syndrome) from trisomy 21?
Malformations are more severe and wide ranging, infants rarely survive past the first year
73
Why is there no y-linked inheritance in males with an x-linked disorder?
Males are typically infertile
74
What features are common to all sex chromosome disorders?
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
75
Where does imprinting typically occur?
in the ovum or the sperm, depending
76
Common indications to test for genetic diseases in older patients
Inherited CA syndromes
Atypically mild monogeneic disease (attenuated CF)
Neurodegenerative disorders
77
What population is commonly seen to have PKU?
scandinavians
78
Huntington diesease is characterized by what clinical manifestations?
Progressive movement disorders and dementia 2/2 degeneration of striatal GABAergic neurons
79
What tissues are commonly involved in EDS?
Skin, ligaments and joints d/t being rich in collagen
80
Clinical features of Prader-Willi syndrome
Mental retardation
Short stature
Hypotonia
Profound hyperphagia
Obesity
Hypogonadism
81
What differentiaties Hunter syndrome from the other forms of MPS?
It is of x-linked inheritance
Does not involve clouding of the cornea
Expresses milder clinical course
82
What has a strong influence on the incidence of trisomy 21?
Maternal age
83
What are the clinical features associated with McArdles disease?
Painful muscle cramps after exercise
Exercise fails to raise blood lactate levels d/t defect in glycolysis
84
Mutations involving single genes follow one of three patterns of inheritance, what are they?
Autosomal dominant
Autosomal recessive
X-linked
85
loss of function mutations arise from what type of mutation?
What does this mutation result in?
An autosomal dominant mutation
Results in the loss of activity of the gene product
86
How does mosaicism arise?
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
87
All mucopolysaccharidoses are inherited through autosomal recessive pattern except which form?
MPS II (Hunter)
88
Causative mutations involving the expansion of trinucleotide repeats usually involve what nucleotides?
Cytosine (C)
Guanine (G)
89
Manifestation of chromosomal disorders?
Arise from structural or numerical alteration in the autosomes and sex chromosomes
90
Tx for PKU
Dietary retrictions, reducing phenylalanine intake
(artificial sweetners often with phenylalanine)
91
What clinical features are common to most types of females with Turner syndrome
Coarctation of the aorta
Short stature
Amenorrhea
Cubitus valgus
Webbing of the neck
Fibrotic (streak) ovaries
92
Functional differences between a paternal allele and a maternal allele arise from?
Genomic imprinting
93
What is the COD of infants and young children with trisomy 21?
Cardiac conditions
94
What is a known enzyme deficiency that is unmasked after taking a specific drug?
Glucose 6-phosphate dehydrogenase leads to severe hemolytic anemia after taking the antimalaria drug Primaquine
95
Anticipation is seen in fragile X syndrome, what does this mean?
Clinical features of fragile X syndrome worsen with each successive generation
96
Clinical manifestations of PKU
phenylalanemia which leads to mental retardation, hypopigmentation of skin and hair, eczema
97
What is the most common chromosomal disorder?
Down syndrome (trisomy 21)
98
Gaucher Disease is caused by a deficiency in what enzyme?
What does it lead to?
Glucocerebrosidase
Accumulation of glucocerebroside in phagocytes, with subsequent activation leading to the release of pro-inflammatory cytokines (IL-1, TNF, IL-6)
99
Gene mutation for Kyphoscoliosis type EDS
Lysyl hydroxylase
100
Characteristics of complex multigenic disorders
Provide examples
Common (polymorphisms)
Low penetrance
Ex: Atherosclerosis, DM, HTN, autoimmune dz, height and weight
101
Characteristics of chromosomal disorders
Uncommon
High penetrance
102
Of the types of Gaucher disease, what form is the most aggressive?
What are the manifestations
Type II
Progressive CNS involvement, hepatosplenomegaly, **early death**
103
What is the most common lysosomal storage disorder?
Gaucher disease
104
What sex chromosome disorder is the most common cause of male infertility?
Klinefelter Syndrome (47, XXY)
105
Regardless of the number of X chromosomes, the presence of a Y chromosome determines the sex of the person to be?
Male
106
Secondary accumulation
Results from impaired autophagy, leading to the accumulation of dysfunctional mitochondria
107
Tay-Sachs disease results from a mutation where?
What does this lead to?
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
What type of mutation gives rise to CA and some congenital malformations?
Somatic cell mutations
109
What are the clinical manifestations of EDS?
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
What is the most distinctive feature in individuals with fragile X syndrome?
macro-orchidism (large testicles)
Observed in 90% of affected prepubertal males
111
Euploid
Any exact multiple of haploid number of chromosomes (23)
112
Mitochondrial disorder inheritance pattern
All affected mothers pass the disease onto all children
Affected males do not pass on the trait
113
The resolution of banding in a karyotype is markedly improved if the cells are obtained in what phase of the cell cycle?
Prophase
114
What are the clinical features of a patient with down syndrome?
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
What are the mechanisms for which loss of fibrillin in Marfan syndrome leads to the clinical manifestations?
loss of structural suppport in microfibril rich CT
Excessive activation of TGF-β signaling
116
What type of mutation gives rise to inherited diseases?
Germ cell mutations
117
True hermaphrodite
contains both ovarian and testicular tissue
118
What pattern of inheritance does CF follow?
Autosomal recessive
119
If an insertion or deletion does not occur in multiples of 3, what happens when the gene is transcribed and translated?
There is a frameshift mutation which typically involves addition of incorrect AA followed by a premature stop codon (truncation)
120
What is the mode of inheritance of EDS?
Encompasses all three modes (AD, AR, x-linked)
121
Predominant population affected by Neimann-Pick dz?
Ashkenazi jews
122
Cause of death in patients with MPS?
MI
Cardiac decompensation
123
Cause of Angelman syndrome?
deletion of maternally derived chromosome 15
15, del(15)(q11.2q13)
124
57% of females with turner syndrome are missing an entire chromosome, what karyotype is this?
45, XO
125
Morphologic changes seen with Gaucher disease
Distended phagocytes (gaucher cells) in liver, spleen, bone marrow, lymph nodes, tonsils, thymus
*Crumpled tissue paper* appearing fibrillary cytoplasm
126
Klinefelter syndrome has what classic karyotype pattern and what genetic defect causes this syndrome?
47, XXY
Meiotic nondisjunction
127
Prader-willi syndrome and Angelman syndrome both arise from deletions on what chromosome?
What makes these syndromes different?
15q12
Whether it is the paternal or maternal chromosome
128
Consequences of enzymatic mutations
accumulation of substrates (galactosemia)
decreased amount of end product (Lesch-nayan sydrome)
failure to inactivate a tissue damaging substrate (α1-antitrypsin def)
129
What percentage of females who are carriers of fragile X syndrome are affected?
30-50%
| (i.e. show mental retardation)
130
Ectopia lentis is so uncommon, that if found (esp bilat) it should raise suspicion for what disorder?
Marfan syndrome
131
What is the single most important cause of primary amenorrhea?
Turner Syndrome
132
Clinical features of DiGeorge syndrome
thymic hypoplasia with resultant T cell immunodeficiency
Parathyroid hypoplasia leading to hypoparathyroidism + hypocalcemia
Cardiac malformations
Mild facial anomalies
Cleft palate
133
Von Gierke Disease is a hepatic glycogen storage disease characterized by the deficiency of what enzyme?
Glucose-6-phosphatase
134
ABO blood type results from what type of mutation?
single base deletion
135
involvement of what tissues dominates the clinical picture of tay-sachs disease?
Neurons and retina
136
Where is the gene mutation that causes cystic fibrosis?
CFTR on chromosome 7q31.2
137
What disease is associated with a deficiency in lysosomal glucosidase (acid maltase)?
Pompe dz
138
CF results from what type of mutation?
base deletion
139
Categories of mechanisms involved in mendelian disorders
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
Why is it difficult to distinguish between a mendelian disorder and a multifactorial disease?
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
Clinical manifestations of tay-sach's disease
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
Isochromosome
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
Clinical features of Angelman syndrome
Mental retardation
Ataxia
Seizures
Inappropriate laughter
"happy puppets"
144
Familial hypercholesterolemia results from a mutation in a receptor, what receptor is this?
LDL
145
What is the most severe form of Niemann pick dz and what are the manifestations?
Type A
Extensive neuro involvement
Marked accumulation of sphingomyelin viscerally
Cherry red spot in retina
Hepatosplenomegaly
**Death by 3 y/o**
146
What is the most common sex chromosome abnormality in females?
Turner syndrome
147
Missense mutation
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
Autosomal recessive disorders are characterized by
mutations in both alleles at a given loci
149
Clinical manifestations of Niemann-Pick dz type C
Ataxia
Vertical supranuclear gaze palsy
dystonia
dysarthria
psychomotor regression
150
Mucopolysaccharidoses result from mutations which lead to
deficient enzymes that degrade glycosaminoglycans, causing a build up of mucopolysaccharides in the ground substance of CT
151
What causes aneuploidy?
Nondisjunction
Anaphase lag
152
What trisomies are similar in karyotype and clinical features to trisomy 21?
Trisomy 18 and trisomy 13
153
Glycogen storage diseases result in hereditary deficiencies in what types of enzymes?
Enzymes responsible for the synthesis or degradation of glycogen
154
Patients with Klinefelter syndrome are at higher risk of developing what other conditions?
Breast CA
Type II DM and metabolic syndrome
Mitral valve prolapse
Osteoporosis
Extragonadal cell tumors
Autoimmune dz such as SLE
155
What is distinct about a PKU patients urine and sweat?
Musty or mousy odor to it
156
Turner sydrome is characterized by?
Hypogonadism in phenotypic females
157
The mutation in the LDL receptor, leading to familial hypercholesterolemia results in what clinical manifestations?
Tendinous Xanthomas
Increased cholesterol which leads to premature atherosclerosis and increased risk of MI
158
What is the most common genetic cause of congenital malformations?
Multifactorial inheritance
159
What type of mutation leads to Niemann-Pick type A?
Missense mutation resulting in complete deficiency of sphingomyelinase
160
Patients with Down syndrome are at a 10-20 fold increased risk at developing what condition?
Acute leukemia
161
Patients with CF prone to getting Infections by what organisms?
* Haemophilus Influenzae*
* Pseudomona aerugionsa*
162
If a patient has an MI at a young age (before 20 y/o), what condition does this raise suspicion for?
homozygotic familial hypercholesterolemia
163
How is mitochondrial DNA transmitted?
Mothers transmit their mtDNA to all offspring (M and F), fathers DO NOT pass on mtDNA
164
Define mutation
a permanent change in the DNA
165
Nondisjunction
Occurs during gametogenesis, a gamete has either an extra chromosome or one less chromosome, result in trisomy or monosomy
166
Neimann-Pick Disease (types A and B)
Lysosomal accumulation of sphingomyelin d/t deficiency in sphingomyelinase
167
What is the most common form of GM2 gangliosidosis?
Tay-Sachs disease
168
How does a robertsonian translocation contribute to Trisomy 21?
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
Common test for CF?
Sweat chloride
170
Treatment options for lysosomal storage diseases
Enzyme replacement therapy
Substrate reduction therapy
Molecular chaperone therapy
171
Velocardiofacial syndrome results from
Chr 22q11.2 deletion syndrome
172
Complex disorders result from
collective inheritance of many polymorphisms
173
What is the second most common cause of mental retardation after Down Syndrome?
Fragile X syndrome
174
What are the characteristics of CF?
abnormal function of the epithelial chloride channel protein, resulting in disorderly ion transport affecting fluid secretions
175
Down syndrome is most commonly cause by what genetic problem?
Meiotic nondisjunction
176
Morphologic changes seen in Tay-Sachs disease
Neurons are dilated with cytoplasmic vacuoles that represent distended lysosomes filled with gangliosides
Whorled lysosomes
177
Ehlers-Danlos Syndrome (EDS) arises from defects in
synthesis or structure of fibrillar collagen
178
If an insertion or deletion occurs in multiples of 3, what happens when the gene is transcribed and translated?
the reading frame remains intact but an abnormal protein is produced
179
What is the threshold effect?
A minimum number of mutatnt mtDNA must be present in a cell or tissue before oxidative dysfunction gives rise to disease
180
What common mucopolysaccharides accumulate in CT?
Dermatan sulfate
Heparan sulfate
Keratan sulfate
Chondroitin sulfate
181
Patients with Chr 22q11.2 deletion syndrome are at high risk of developing what condition?
Psychiatric disorders including schizophrenia and bipolar disorder
182
Where is the mutation that causes Niemann-pick type C?
NPC1 gene responsible for producing NPC1 involved in cholesterol transport from the lysosome
183
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?
Selectively binds mRNAs associated with polysomes and regulates their intracellular transport to dendrites
Acts as a translation regulator
184
Leber Hereditary Optic Neuropathy (LHON) is a mitochondrial disorder characterized by
progressive bilateral loss of central vision
185
How many cases of Trisomy 21 can be attributed to a Robertsonian translocation?
~4%
186
Characteristics of mendelian disorders?
alterations in a single gene leading to abnormal product or a decrease in the amount of normal product produced
187
Why is mtDNA of maternal inheritance?
the ova contain numerous mitochondria while spermatozoa contain few, if any, mitochondria
188
Clinical features of Klinefelter Syndrome (47, XXY)
Eunuchoid body habitus with abnormally long legs
Small testes and small penis
lack of male secondary sex characteristics (deep voice, facial hair)
Gynecomastia
189
What morphologic changes are seen in pompe disease?
Cardiomegaly leads to cardiorespiratory failure and **death** within 2 yrs
Hepatomegaly (mild)
190
What type of mutation leads to cystic fibrosis?
3 base deletion
191
Primary accumulation
deficiency in lysosomal enzyme renders a substrate incompletely catabolized, leading to the accumulation of the metabolite within the lysosome
192
Paternal imprinting results in?
Paternal allele being inactivated (silenced)
193
Indications for prenatal testing of fetuses at risk for cytogenetic abnormality
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
What trinucleotide repeat is seen with huntington disease?
CAG
195
196
What is the most important cauese of increased mortality in children with turner syndrome?
Cardiovascular abnormalities
| (typically left sided)
197
Characteristics of a mendelian disorder?
Rare
Highly penetrant
Ex: sickle cell anemia
198
In what population is Tay-sachs disease common?
Eastern european populations
Ashkenazi Jews
199
Sex-linked disorders follow what pattern of inheritance?
x-linked
often recessive
200
Incomplete penetrance
Individual has the mutation but has a normal phenotype
201
Mutations in promotor or enhancer sequences leads is a noncoding mutation which results in what?
Inability of the transcription factors to bind leading to decreased transcription and translation
202
The most severely affected infants with Turner syndrome present with what clincial features?
Swelling of the feet and hands
Cystic hygroma that eventually subsides, leaving bilateral neck webbing
203
What is the most common autosomal recessive form of EDS?
Kyphoscoliosis type
204
What are the 3 subgroups of glyocgen storage diseases?
Hepatic type
Myopathic type
Miscellaneous (aspects of both above)
205
Anticipation
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
What disease is caused by trinucleotide repeats occurring during spermatogenesis?
Huntington disease
207
What is the most common lethal genetic disease that affects caucasian populations?
Cystic Fibrosis
208
Categories of single gene disorders with nonclassical inheritance patterns
Diseases caused by trinucleotide repeats
Disorders caused by mutations in mitochondrial genes
disorders associated with genomic imprinting
Disorders associated with gonadal mosaicism
209
When is a gene termed polymorphic?
When it has two alleles, each of which occurs at a frequency of at least 1% in the population
210
Morphologic changes seen in Niemann-Pick disease
Enlarged cells
Foamy cytoplasm
Zebra bodies (lysosomes with concentric lammellations)
Vacuolation of neurons
Some have cherry red spot on retina
211
DiGeorge syndrome results from what?
Results from Chr 22q11.2 deletion syndrome
212
Maternal imprinting results in?
Transcriptional silencing of the maternal allele
213
Three key mechanisms by which unstable repeats cause disease
Loss of function
Toxic gain of function
Toxic gain of function mediated by mRNA
214
Clinical manifestations of Marfan syndrome
Tall with long extremities
Double jointed
Frontal bossing
Ectopia lentis
Aortic dissection
215
What disorder is an example of variable expressivity?
Neurofibromatosis type 1
216
What are the clinical features associated with cystic fibrosis?
Abnormally viscous secretions
chronic lung dz (emphysema and bronchiectasis)
Pancreatic insufficiency
Steatorrhea
Cirrhosis
Meconium ileus
Male infertility
217
What common malformations are considered to be of multifactorial inheritance?
Cleft lip and cleft palate
Neural tube defects
218
What two disorders are common in Ashkenazi Jews and also present clinically with cherry red spot in the macula?
Tay Sachs disease
Niemann-Pick types A and B
