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518 Chapter 14: Genetic syndromes

Table 14.2 Examples of autosomal dominant inherited conditions
Disease Locus Gene
Congenital adrenal 6p Multiple 21-hydroxylase deficiency results in virilisation, and renal salt wasting in severe cases
hyperplasia (21-OH)
Phenylketonuria 12q PKU1 Deficiency phenylalanine hydroxylase causing mental retardation if untreated
Sickle cell disease 11p Hbβ Sickling of red blood cells in hypoxia
Cystic fibrosis 7q CFTR Abnormalities in chloride channel results in thickened secretions in multiple organs
Gaucher disease I 1q GBA Mutations in the acid-β glucosidase gene results in hypersplenism, and bone lesions.
Particularly common in Ashkenazi Jews
Tay Sachs disease 15q Hexa Lysosomal storage disease causing accumulation in GM2 ganglioside and
progressive neurodegeneration
Galactosaemia 9p GALT Galactose-1-phosphate uridylyl-transferase mutation causing jaundice,
hepatomegaly and mental retardation if untreated
Wilson disease 13q ATP7B Abnormal copper transporting protein causing Kayser–Fleischer rings, cirrhosis,
hepatomegaly, tremor and dementia if left untreated

Unaffected Male
Affected Male
Unaffected Female
Carrier Female

Figure 14.3 X-linked recessive
inheritance.

Table 14.3 X-linked conditions
Disease Inheritance Gene
Bruton Recessive BTK Mutations in Bruton agammaglobulinaemia tyrosine
agammaglobulinaemia kinase gene leads to absent B and plasma cells.
Chronic granulomatous Recessive Cytochrome Neutrophils can phagocytose material, but are unable
disease b245 to generate respiratory burst and hence kill bacteria.
Duchenne muscular dystrophy Recessive Dystrophin Progressive proximal muscle weakness with calf
psuedohypertrophy. Dystrophin is a cytoskeletal
protein found in muscle cells, which normally acts
to anchor the cell membrane to the ECM.
Glucose-6-phosphate Recessive G6PD Highly polymorphic gene, so females may inherit
dehydrogenase deficiency 2 genes with low activity and hence be affected;
causes congenital non-spherocytic haemolytic
anaemia.
Fragile X syndrome Female ‘carriers’ may FMR1 Expanded (CGG)n repeat in the fragile X mental
also be affected retardation 1 gene; unstable if > 52 repeats;
symptomatic if > 200 repeats. Exhibits genetic
anticipation.
X linked hypophosphataemia Dominant PHEX Hypophosphataemic vitamin D resistant rickets.
Rett syndrome Dominant MECP2 Females only affected, thought to be lethal in-utero to
males. Causes progressive intellectual deterioration,
loss of purposeful use of hands and jerky truncal
ataxia.