Adult polycystic kidney disease

Adult polycystic kidney disease (APKD) is typically a late onset,
autosomal dominant disorder characterised by multiple renal
cysts. It is one of the most common genetic diseases in humans
and the incidence may be as high as 1 in 1000. There is
considerable variation in the age at which end stage renal
failure is reached and the frequency of hypertension, urinary
tract infections, and hepatic cysts. Approximately 20% of APKD
patients have end stage renal failure by the age of 50 and 70%
by the age of 70, with 5% of all end stage renal failure being due
to APKD. A high incidence of colonic diverticulae associated
with a risk of colonic perforation is reported in APKD patients
with end stage renal failure. An increased prevalence of 4–5%
for intracranial aneurysms has been suggested, compared to the
prevalence of 1% in the general population. There may also be
an increased prevalence of mitral, aortic and tricuspid
regurgitation, and tricuspid valve prolapse in APKD.

affected individuals have renal cysts d

All affected individuals have renal cysts detectable on
ultrasound scan by the age of 30. Screening young adults at risk
will identify those asymptomatic individuals who are affected
and require annual screening for hypertension, urinary tract
infections and decreased renal function. Children diagnosed
under the age of one year may have deterioration of renal
function during childhood, but there is little evidence that
early detection in asymptomatic children affects prognosis.

locus heterogeneity in APKD

There is locus heterogeneity in APKD with at least three loci
identified by linkage studies and two genes cloned. The gene
for APKD1 on chromosome 16p encodes a protein called
polycystin-1, which is an integral membrane protein involved in
cell–cell/matrix interactions. The protein encoded by the gene
for APKD2 on chromosome 4 has been called polycystin-2.
Mutation analysis is not routinely undertaken, but linkage
studies may be used in conjunction with ultrasound scanning to
detect asymptomatic gene carriers.

Severe congenital deafness

Severe congenital deafness affects approximately 1 in 1000
infants. This may occur as an isolated deafness as or part of a
syndrome. At least half the cases of congenital deafness have a
genetic aetiology. Of genetic cases, approximately 66% are
autosomal recessive, 31% are autosomal dominant, 3% are
X linked recessive. Over 30 autosomal recessive loci have been
identified. This means that two parents with autosomal
recessive congenital deafness will have no deaf children

Connexin 26 mutations

Mutations in the connexin 26 gene (CX26) on chromosome 13
have been found in severe autosomal recessive congenital
deafness and may account for up to 50% of cases. One specific
mutation, 30delG accounts for over half of the mutations
detected. The carrier frequency for CX26 mutations in the
general population is around 1 in 35. Mutation analysis in
affected children enables carrier detection in relatives, early
diagnosis in subsequent siblings and prenatal diagnosis if
requested.

The CX26 gene

The CX26 gene encodes a gap junction protein that forms
plasma membrane channels that allow small molecules and
ions to move from one cell to another. These channels play a
role in potassium homeostasis in the cochlea which is
important for inner ear function.

Pendred syndrome

Pendred syndrome is an autosomal recessive form of deafness
due to cochlear abnormality that is associated with a thyroid
goitre. It may account for up to 10% of hereditary deafness.
Not all patients have thyroid involvement at the time the
deafness is diagnosed and the perchlorate discharge test has
been used in diagnosis.
The gene for Pendred syndrome, called PDS, was isolated in
1997 and is located on chromosome 7. The protein product
called pendrin, is closely related to a number of sulphate
transporters and is expressed in the thyroid gland. Mutation
detection enables diagnosis and carrier testing within affected
families.