Outcome of intracytoplasmic sperm injection for a couple in which the man is carrier of CFTR p.[R74W;V201M;D1270N] and p.P841R mutations and his spouse a heterozygous carrier of p.F508del mutation of the cystic fibrosis transmembrane conductance regulator gene.
OBJECTIVE
To document the phenotype associated with the p.[R74W;V201M;D1270N] and p.P841R mutations of cystic fibrosis transmembrane conductance regulator (CFTR) gene.


METHODS
Case report.


METHODS
Biology and medicine of reproduction in a university hospital.


METHODS
A couple in which the man is carrier of the triple mutant p.[R74W;V201M;D1270N] allele in trans to p.P841R mutation and his spouse a heterozygous carrier for the severe p.F508del mutation of the CFTR gene, who became pregnant after intracytoplasmic sperm injection (ICSI) with twins.


METHODS
Genetic counseling; CFTR gene sequencing; ICSI; children's follow-up.


METHODS
First report of a male phenotype associated with the p.P841R mutation.


RESULTS
The triple mutant p.[R74W;V201M;D1270N] allele associated with the unknown p.P841R mutations were detected in this man with congenital bilateral absence of the vas deferens, which may presume p.P841R as a severe mutation. After genetic counseling, the couple preferred prenatal diagnosis after ICSI than preimplantation genetic diagnosis, which revealed that the boys were both carriers of p.[R74W;V201M;D1270N] and p.F508del mutations. They are now 4 years old and show normal growth without nutritional deficiency.


CONCLUSIONS
This case report documents for the first time a male phenotype associated with the p.P841R mutation and underlines the difficulties in counseling a man with congenital bilateral absence of the vas deferens carrying uncommon mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene before ICSI.
Brugnon
Florence
F
CHU Clermont-Ferrand, Biologie du Développement et de la Reproduction, CECOS, Hôtel Dieu, Clermont Ferrand, France. fbrugnon@chu-clermontferrand.fr
Bilan
Frederic
F
Heraud
Marie-Christine
MC
Grizard
Genevieve
G
Janny
Laurent
L
Creveaux
Isabelle
I
D000328:Adult; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D050498:Live Birth; D008297:Male; D009154:Mutation; D010641:Phenotype; D011247:Pregnancy; D011272:Pregnancy, Multiple; D011296:Prenatal Diagnosis; D020554:Sperm Injections, Intracytoplasmic; D014427:Twins; D014564:Urogenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D014649:Vas Deferens / Q000002:abnormalities*
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator