Genetics Flashcards
Which type of Ehlers-Danlos syndrome is most popular?What is the mode of inheritance?
What is the mechanism of the defect?
What are the typical clinical features?
Type 4: Kyphoscoliosis
Autosomal recessive
Defect in lysyl hydroxylase causes decreased hydroxylation of lysine residues during collagen synthesis.
Joint laxity, congenital scoliosis, hypotonia, and ocular fragility
What is Ehlers-Danlos Syndrome?
Genetic disorder causing some defect in fibrillar collagen synthesis/ structure
Involves tissues rich in collagen (skin, ligaments, joints)
What is Marfan Syndrome?
Inherited defect in fibrillin-1 causing abnormalities in tissues requiring elastin
What are the clinical manifestations of Marfan Syndrome
Loss of structural support in microfibril rich connective tissues Excessive activation of TGF-B signaling Mitral valve lesions Aortic lesions Lens dislocations Unusually tall with long digits
what chromosome does the defect occur for Marfan Syndrome?
chromosome 15
Which lysosome storage disorders target Ashkenzaic Jews?
Tay-Sachs
Neimann-Pick
Most common lysosomal storage disorder
Gaucher Disease
Defect in Hexosaminidase A
Tay-Sachs
what chormosome is associated with Tay-Sach Disease
Chromosome 15
Life expectancy of Tay-Sachs patient
<3 years
Morphology characteristic of Neimann-Pick
foamy macrophages
What chromosome is associated with Neimann-Pick
chromosome 11
what protein is deficient in Neimann-Pick
Sphingomyelinase
Differences between types of Neimann-Pick
Infantile: includes neurologic involvement, life expectancy ~3 years
Adult: only organomegaly and usually survive into adulthood
What protein is mutated in Gaucher Disease?
Glucocerebrosidase
Signs of Gaucher Disease
splenomegaly
expansion of bone marrow space
CNS involvement
47 XXY or 48XXXY
Kleinfelter Syndrome
Associations of Kleinfelter Syndrome
mitral valve prolapse osteoporosis breast cancer extragonadal tumors SLE
Clinical manifestations of Kleinfelter Syndrome
tall gynecomastia poor muscle tone reduced testosterone but high FSH lower IQ than siblings
Mechanism of Fragile X Syndrome
long repeating sequences of 3 nucleotides caused by mutation of FMR1 gene
The more the repeats exceed 230, the more the chromosome becomes abnormally methylated, promoting transcrptional suppression of FMR-1
Abscence of FMRP leads to phenotypic changes
Highest cause of mental retardation
Down Syndrome
second highest cause of mental retardation
Fragile X syndrome
which chromosome is involved in Angelmann and Prader-Willi syndrome
15q12
which gene is active in Angelmann syndrome
Prader willi
which gene is imprinted in Prader willi syndrome
prader willi
what is genetic imprinting
normal selective inactivation of maternal or paternal alleles, usually via methylation or deacetylation
Deletion of maternal 15q12
Angelmann Syndrome
Deletion of Paternal 15q12
Prader-Willi Syndrome
physical features of prader willi
short stature mental retardation hypotonia hyperphagia hypogonadism small hands/ feet
physical features of Angelmann syndrome
ataxic gait
seizure= inappropriate laughter
mental retardation
What protein is defective in Classic Galactosemia
Gal-1-Phosphate Uridyl Transferase
What is Cystic Fibrosis
defective CF gene causes malfunction of exocrine glands, leading to increased mucous viscosity and chronic pulmonary disease
what ion is increased in the secretions of CF patients
Chloride
Most common clinically encountered inborn error of amino acids
PKU
what enzyme is defective in PKU?
Phenylalanine hydroxylase
characteristics of PKU
decreased pigmentation
musty body odor
microcephaly
mental deterioration
What else could cause PKU?
deficiencies in enzymes needed to produce BH4 or BH2 reductase
What causes Maple Syrup Urine Disease
defects in proteins composing branched chain alpha ketoacid dehydrogenase complex
characteristics of MSUD
maple syrup odor to urine high urinary levels of ketoacids, isoleucine and valine mental/ physical disability feeding problems neonatal death
What causes albinism
defective tyrosine metabolism to DOPA
What enzyme is defective in homocystinuria?
Cystathionine Beta synthase
what cofactor is needed to produce cystathionine
PLP (B6)
characteristics of homocystinuria
lens dislocation
increased risk of thrombi
high serum and urine homocysteine
intellectual disability
What accumulates in Alkaptonuria
homogentisic acid
What causes Alkaptonuria
incomplete metabolism of Phenylalanine and Tyrosine due to homogentisic oxidase
characteristics of Alkaptonuria
dark urine on standing
defective cardiac valves
dark pigmentation od fibrous tissues and cartilage
