RESUMO
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.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Doenças Urogenitais Masculinas/genética , Diagnóstico Pré-Natal , Criança , Pré-Escolar , Fibrose Cística/complicações , Fibrose Cística/patologia , Feminino , Heterozigoto , Humanos , Lactente , Recém-Nascido , Infertilidade Masculina/complicações , Infertilidade Masculina/genética , Masculino , Doenças Urogenitais Masculinas/complicações , Doenças Urogenitais Masculinas/patologia , Mutação , Taxa de Mutação , Fenótipo , Suor/química , Ducto Deferente/anormalidades , Ducto Deferente/patologiaRESUMO
OBJECTIVES: Insufficient gynecological follow-up and cervical screening has been reported in women with cystic fibrosis (CF). Some of these patients will require a pulmonary transplantation, known to be associated with a higher risk of cervical dysplasia. The aim of this study was to explore the results of cervical screening in adult women with CF, and to report the prevalence of abnormal pap smear tests in this population. STUDY DESIGN: We retrospectively analyzed medical records of sexually active women with CF who attended a gynecological consultation in Lyon University CF referral center between June 2014 and December 2015. The primary outcome was the result of the pap smear test. RESULTS: Forty-seven women (32 non-transplanted and 15 transplanted) were included in the study. The median age of the patients was 28 (range 18-53). The clinical examination revealed that 20 (42.5%) women presented an abnormality (inflammatory cervix, cervical or vulvovaginal condyloma). An abnormal pap smear was found in 8/32 (25%) non transplanted women and in 5/15 (33.3%) transplanted women, with no significant difference between the two groups (p=0.75): seven atypical squamous cells of undetermined significance (ASC-US), five low grade squamous intraepithelial lesion (LSIL), one atypical glandular cells (AGC). Six (12.8%) (four non transplanted, and two transplanted) women had an histologically proven dysplasia (four Cervical Intraepithelial Neoplasia (CIN)1, one CIN2, and one endocervical adenocarcinoma in situ). Overall, ten (21.3%) women had a Human Papilloma Virus (HPV) related disease (cervical and/or vulvovaginal). CONCLUSION: A high proportion of transplanted and non-transplanted women with CF had abnormal pap smear tests and cervical dysplasia. A regular gynaecological follow-up, periodic cervical screening, and routine HPV vaccination are strongly recommended in this population.