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CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders
- Source :
- Journal of Medical Genetics, Journal of Medical Genetics, BMJ Publishing Group, 2013, 50 (4), pp.220-227. ⟨10.1136/jmedgenet-2012-101427⟩, Journal of Medical Genetics, 2013, 50 (4), pp.220-227. ⟨10.1136/jmedgenet-2012-101427⟩
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- International audience; BACKGROUND:The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.METHODS:Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.Arg117His and a second CFTR mutation referred for symptoms or family history, by all French molecular genetics laboratories, referring physicians, CF care centres and infertility clinics.RESULTS:97% of the patients had the intronic T7 normal variant in cis with p.Arg117His. 89% patients were male, with CBAVD being the reason for referral in 76%. In 166/179 patients with available detailed clinical features, final diagnoses were: four late-onset marked pulmonary disease, 83 isolated CBAVD, 67 other CFTR-related phenotypes, including 44 CBAVD with pulmonary and/or pancreatic symptoms and 12 asymptomatic cases. Respiratory symptoms were observed in 30% of the patients, but the overall phenotype was mild. No correlation was observed between sweat chloride concentrations and disease severity. Five couples at risk of CF offspring were identified and four benefited from prenatal or preimplantation genetic diagnoses (PND or PGD). Eight children were born, including four who were compound heterozygous for p.Arg117His and one with a severe CF mutation.CONCLUSIONS:Patients with CBAVD carrying p.Arg117His and a severe CF mutation should benefit from a clinical evaluation and follow-up. Depending on the CBAVD patients' genotype, a CFTR analysis should be considered in their partners in order to identify CF carrier couples and offer PND or PGD
- Subjects :
- Infertility
Male
medicine.medical_specialty
Heterozygote
Cystic Fibrosis
Offspring
[SDV]Life Sciences [q-bio]
Cystic Fibrosis Transmembrane Conductance Regulator
Gene mutation
Compound heterozygosity
Asymptomatic
Cystic fibrosis
03 medical and health sciences
0302 clinical medicine
Vas Deferens
Male Urogenital Diseases
Mutation Rate
Internal medicine
Prenatal Diagnosis
Genotype
Genetics
medicine
Humans
Family history
Child
Sweat
Genetics (clinical)
Infertility, Male
030304 developmental biology
0303 health sciences
business.industry
Infant, Newborn
Infant
medicine.disease
3. Good health
Phenotype
030228 respiratory system
Child, Preschool
Immunology
Mutation
Female
medicine.symptom
business
Subjects
Details
- Language :
- English
- ISSN :
- 00222593 and 14686244
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics, Journal of Medical Genetics, BMJ Publishing Group, 2013, 50 (4), pp.220-227. ⟨10.1136/jmedgenet-2012-101427⟩, Journal of Medical Genetics, 2013, 50 (4), pp.220-227. ⟨10.1136/jmedgenet-2012-101427⟩
- Accession number :
- edsair.doi.dedup.....74af8dc7426831fe5513473ce9708dcb
- Full Text :
- https://doi.org/10.1136/jmedgenet-2012-101427⟩