RESUMEN
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.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Enfermedades Urogenitales Masculinas/genética , Diagnóstico Prenatal , Niño , Preescolar , Fibrosis Quística/complicaciones , Fibrosis Quística/patología , Femenino , Heterocigoto , Humanos , Lactante , Recién Nacido , Infertilidad Masculina/complicaciones , Infertilidad Masculina/genética , Masculino , Enfermedades Urogenitales Masculinas/complicaciones , Enfermedades Urogenitales Masculinas/patología , Mutación , Tasa de Mutación , Fenotipo , Sudor/química , Conducto Deferente/anomalías , Conducto Deferente/patologíaRESUMEN
Men with mutations in LHB, the gene encoding the beta subunit of luteinizing hormone (LHB), have azoospermia with absent or few fetal Leydig cells. We report a mutation in LHB in a man and his sister. The man presented with absence of virilization, undetectable luteinizing hormone, and a low serum testosterone level. He had complete spermatogenesis with a normal sperm count. The mutant luteinizing hormone had a low level of partial activity in vitro. We concluded that the residual luteinizing hormone activity, resulting in the expression of steroidogenic enzymes in few mature Leydig cells producing small amounts of intratesticular testosterone (20.2 ng per gram), was sufficient for complete and quantitatively normal spermatogenesis.
Asunto(s)
Hormona Luteinizante de Subunidad beta/genética , Mutación , Espermatogénesis , Adulto , Femenino , Humanos , Hormona Luteinizante/deficiencia , Hormona Luteinizante/metabolismo , Masculino , Linaje , Análisis de Secuencia de ADN , Testículo/citología , Testosterona/deficienciaRESUMEN
BACKGROUND: Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene have been widely detected in infertile men with congenital bilateral absence of the vas deferens (CBAVD). Despite extensive analysis of the CFTR gene using varied screening methods, a number of cases remain unsolved and could be attributable to the presence of large gene rearrangements, as recently shown for CF patients. METHODS: We carried out a complete CFTR gene study in a group of 222 CBAVD patients with strict diagnosis criteria and without renal anomaly, and searched for rearrangements using a semi-quantitative assay in a subgroup of 61 patients. RESULTS: The overall mutation detection rate was 87.8%, and 82% of patients carried two mutations. Ten out of the 99 different mutations accounted for 74.6% of identified alleles. Four large rearrangements were found in patients who already carried a mild mutation: two known partial deletions (exons 17a to 18 and 22 to 23), a complete deletion and a new partial duplication (exons 11 to 13). The rearrangements accounted for 7% of the previously unknown alleles and 1% of all identified alleles. CONCLUSIONS: Screening for rearrangements should be part of comprehensive CFTR gene studies in CBAVD patients and may have impacts on genetic counselling for the patients and their families.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Reordenamiento Génico/genética , Asesoramiento Genético , Conducto Deferente/anomalías , Francia , Eliminación de Gen , Genotipo , Humanos , Masculino , MutaciónRESUMEN
Phyllodes tumours of the prostate are very rare tumours, as less than 40 cases have been reported in the literature. The authors report the case of a 28-year-old man managed for a phyllodes tumour of the prostate diagnosed in a context of haemospermia. The diagnosis was established by ultrasound, CT MRI and prostatic biopsies. Radical prostatectomy was performed after multidisciplinary discussion. Thirty six months after the operation, the patient was in complete remission, with spontaneous erections and had fathered a child conceived by medically assisted procreation. The authors stress the importance of nerve-sparing radical surgery and early sexual rehabilitation.