Genotype 7T/7T

Question

My husband was tested for mutations in the CFTR gene, and in the results it writes: “ the genotype 7T/7T was detected in the sample in relation to the polymorphic region of the CFTR gene”.
Does the above mean that my husband is a carrier of the disease?
The reason for him being tested was oligoaspermia.

Answer

Dear friend,
Because the congenital bilateral absence of the vas deferens (CBVAD), as well as various abnormalities of spermatogenesis (oligoaspermia), are connected with the presence of cystic fibrosis (CF) mutations in the CFTR gene, a high percentage (70-90%) of males with CBVAD will present abnormalities in the CF gene (Cuppers H & Cassiman JJ 2004, Clauster 2005).
CBVAD is responsible for 3% of male sterility. The frequency of CBVAD is estimated round 1/1000.
Of great importance to the CBVAD is the allele IV8-T5, which is found in 5% of the CFTR genes and is considered to be the most frequent “mild” CFTR allele worldwide. Its frequency in males with CBVAD is 25-40%, that is 5-8 times higher than in the normal male population.
The mechanisms, through which the mutations and polymorphisms act in the pathogenesis of CBVAD are not yet fully understood.
The CF gene is made out of 27 codifying areas which are named exons. The parts between the exons are non codifying regions (they do not synthesise the CF protein) and are named introns.
When the CFTR gene is transported inside the cell nucleus, in order to produce the CFTR protein, the messenger RNA (mRNA) is used, which serves as a matrix for the production of the CFTR protein (the non codifying areas are omitted). There is a region at intron 8 of the CFTR gene, the poly T(n)) area, which affects the gene function through the abnormal splicing of exons 8 and 9. This region at the splicing point can have three forms, 5T, 7T and 9T. During the transcription process in people with different alleles 5T, 7T and 9T, the percentage of incomplete transcription is reverse to the number of T alleles.
7T and 9T are considered to be polymorphic variations, whereas 5T are considered to be mutations of variable penetration.
The poly T(n) region is checked in male adults for genetic assessment due to CBVAD, or when the mutation R117H has been detected.
Therefore, if only 7T/7T was detected in your husband and no other CFTR mutation, your husband is not carrier of the disease (assumed that there is no other rare mutation present that could not be detected with the test), this finding on its own can even not explain the oligoaspermia.
Yours friendly,

Dr. Stavros Doudounakis

19.09.2015