Last update: 22/09/2006
Background to disease
OMIM 219700
Defective membrane ion transport in epithelial cells underlies cystic fibrosis (CF), which is considered to be the most frequent genetic disorder in populations of Caucasian origin. The clinical spectrum is variable. CF can be fatal in childhood or present with only mild symptoms in adulthood. Commonly, there is disruption of exocrine pancreatic, intestinal, bronchial, and sweat gland function resulting in insufficiency of pancreatic enzymes, intestinal obstruction, chronic lung infections, and abnormally high sweat electrolytes. Infertility occurs in males, typically due to absence of vas deferens, and females.
Classical CF is caused by mutations in both copies the CFTR gene and shows an autosomal recessive pattern of inheritance, with a carrier frequency in the range of 1/20-1/30 in the UK (Caucasians). CF has been documented in ethnic groups, including the British Pakistani population in Yorkshire. The commonest mutation in Caucasians is, by far, p.Phe508del (also known as F508del or deltaF508); all other mutations are rare with local variations in frequency. In the Caucasian population of Yorkshire p.Phe508del accounts for ~77% of all CFTR mutations. Certain other mutations are also assayed and the overall mutation detection sensitivity is estimated to be ~88%. See our routine mutation panel (mutations tabulated using both the modern and the traditional nomenclature).
The product of the CFTR gene functions as a transmembrane chloride channel while controlling other transport pathways as well. Mutations in CF cause partial or complete loss of function through various mechanisms.
Laboratory Analysis
Contact scientist: Lampros Mavrogiannis
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|
Test |
Target reporting time (working days) |
|
1. |
10 |
|
|
2. |
Intron 8 poly(T) typing or exon 10 sizing |
10 |
|
3. |
Sequencing of specific exons (known mutations) |
40 |
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4. |
Analysis of 3 linked markers |
10 |