Analysis by mass spectrometry of 100 cystic fibrosis gene mutations in 92 patients with congenital bilateral absence of the vas deferens.
BACKGROUND
Limited mutation analysis for congenital bilateral absence of the vas deferens (CBAVD) has revealed only a minority of men in whom two distinct mutations were detected. We aimed to determine whether a more extensive mutation analysis would be of benefit in genetic counselling and prenatal diagnosis.


METHODS
We studied a cohort of 92 men with CBAVD using mass spectrometry and primer oligonucleotide base extension to analyse an approximately hierarchical set of the most common 100 CF mutations.


RESULTS
Analysis of 100 CF mutations identified 33/92 (35.9%) patients with two mutations and 29/92 (31.5%) with one mutation, compound heterozygosity accounting for 94% (31/33) of those with two mutations. This panel detected 12.0% more CBAVD men with at least one mutation and identified a second mutation in >50% of those considered to be heterozygotes under the two routine 25 mutation panel analyses.


CONCLUSIONS
Compound heterozygosity of severe/mild mutations accounted for the vast majority of the CBAVD patients with two mutations, and underscores the value of a more extensive CF mutation panel for men with CBAVD. The CF100 panel enables higher carrier detection rates especially for men with CBAVD, their partners, partners of known CF carriers, and those with 'mild' CF with rarer mutations.
Wang
Zhenyuan
Z
Center for Human Genetics and the Departments of Pediatrics and Urology, Boston University School of Medicine and Boston Medical Center, Boston, MA 02118, USA.
Milunsky
Jeff
J
Yamin
Moshe
M
Maher
Thomas
T
Oates
Robert
R
Milunsky
Aubrey
A
D000013:Congenital Abnormalities / Q000235:genetics; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009154:Mutation / Q000235:genetics*; D014649:Vas Deferens / Q000002:abnormalities*
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator