Genetic disorders Flashcards
Cystic Fibrosis
- AR
- Disorder of epithelial transport affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, GI and reproductive tracts
- Mutation in CFTR gene, encoding an epithelial chloride channel -> decreased reabsorption of sodium chloride
- Viscous secretions accumulate in respiratory passages -> increased infection risk
- Hypertonic (salty) sweat
Phenylketonuria
- AR inheritance lacking PAH (phenylalanine hydroxylase)
- Features: mental retardation, neurologic abnormalities, decreased skin pigmentation
Galactosemia
- AR
- Lack of GALT -> galactose-1-phosphate accumulates in all tissues
- Fatty change causes early onset hepatomegaly, eventually progressing to cirrhosis
Lysosomal storage disease
- AR
- Defect in lysosomal function -> storage of undigested material
- Clinical: CNS involvement, neruonal damage
Tay-Sachs disease
- AR
- Gangliosidosis (gangliosides accumulate)
- Clinical: mental retardation, blindness, motor weakness
Glycogen storage disease
- AR
- Accumulation of glycogen
- Type I (hepatic; von Gierke): liver enlargement; not G-6-phosphatase
- Type II (Pompe): type of lysosomal storage disease
- Type V (McArdle): deficiency of muscle phosphorylase
Fragile X syndrome
- Trinucleotide (CGG) repeats in the FMR gene
- LOF mutation
- Clinical: mental retardation, abnormal facial features
3 most relevant trisomies
Trisomy 21 - Downs
Trisomy 18 - Edwards
Trisomy 13 - Patau
- All are associated with mental retardation
Genetic background of Cri du chat syndrome
Partial deletion of the short arm of chromosome 5
22q11.2 deletion syndrome
Causes a spectrum of disorders, among them DiGeorge syndrome, characterized by:
- T cell immunodeficiency
- Hypocalcemia, which can lead to severe heart defects
Klinefelter syndrom
- XXY karyotype
- Male hypogonadism
- Elongated body
- Infertility
Turner syndrome
- X monosomy
- Growth retardation accompanied by other congenital malformations
Disease caused by triplet repeat mutations
- Fragile X syndrome: CGG
- Huntington’s: CTG; GOF mutation
Disease(s) caused by mitochondrial gene mutations
- Maternal inheritance only
- Most common example is Leber congenital neuropathy, characterized by progressive loss of vision
Diseases due to changes of imprinted regions of genome
Prader-Willi: only paternal genes are expressed
Angelman syndrom: only maternal genes are expressed
- Deletions are on the same chromosomal region: band q on chromosome 15
- Both are associated with mental retardation
