[Role of deep seminal tract imaging in the diagnosis of unilateral agenesis of the vas deferens. Case report of a patient with CFTR gene mutation]. / Place de l'imagerie des voies séminales profondes dans le diagnostic d'une agénésie déférentielle unilatérale: à propos d'un patient ayant des mutations du gène CFTR.

The authors report the cases of a 35-year-old man with a 4-year history of primary infertility with normal clinical examination and semen parameters. Deep genital tract imaging demonstrated isolated unilateral agenesis of the pelvic portion of the left vas deferens associated with abnormalities of the homolateral seminal vesicle. Molecular analysis of the CFTR gene demonstrated composite heterozygosity with the presence of DeltaF508 / V938G mutations. In the light of this case, the authors recommend urogenital imaging for all men consulting for infertility.

CFTR genotypes in patients with normal or borderline sweat chloride levels.

In recent years, some patients bearing "atypical" forms of cystic fibrosis (CF) with normal sweat chloride concentrations have been described. To identify the spectrum of mutant combinations causing such atypical CF, we collected the results of CFTR (ABCC7) mutation analysis from 15 laboratories. Thirty patients with one or more typical symptoms of the disease associated with normal or borderline sweat chloride levels and bearing two CFTR mutations were selected. Phenotypes and genotypes of these 30 patients are described. A total of 18 different CFTR mutations were observed in the 60 chromosomes analysed. F508del was present in 31.6 % of the mutated chromosomes and 3849+10kbC>T in 13.3 %. R117H, D1152H, L206W, 3272-26A>G, S1235R, G149R, R1070W, S945L, and the poly-T tract variation commonly called IVS8-5T were also observed. The relative frequency of CFTR mutations clearly differed from that observed in typical CF patients or in CBAVD patients with the same ethnic origin. A mild genotype with one or two mild or variable mutations was observed in all the patients. These findings improve our understanding of the distribution of CFTR alleles in CF with normal or borderline sweat chloride concentrations and will facilitate the development of more sensitive CFTR mutation screening.

Analysis of the thyroid phenotype in 42 patients with Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct.

BACKGROUND: Pendred syndrome (PS), a recessive disorder caused by mutations in the SLC26A4 (PDS) gene, is associated with deafness and goiter. SLC26A4 mutations have also been identified in patients exhibiting isolated sensorineural hearing loss without apparent thyroid abnormality (nonsyndromic enlargement of the vestibular aqueduct; nonsyndromic EVA). Our aim was to describe systematically the thyroidal phenotypes and the SLC26A4 genotypes of patients presenting with PS or nonsyndromic EVA. METHODS: Nineteen patients with PS and 23 patients with nonsyndromic EVA, aged 5-53 years, were included. They underwent thyroid evaluation (physical examination, biological thyroid function tests, measurement of thyroglobulin level, thyroid ultrasonography, and thyroid (123)I scintigraphy with perchlorate discharge test), otological evaluation, and SLC26A4 mutation screening. RESULTS: In 19 patients with PS, goiter was identified in 15 (79%) and hypothyroidism in 15 (79%); hypothyroidism was subclinical in four patients and congenital in six patients. The perchlorate discharge test (PDT) was positive in 10/16 (63%). Morphological evaluation of the inner ear using MRI and/or CT showed bilateral EVA in 15/15 PS patients. Mutation screening revealed two SLC26A4 mutant alleles in all 19 PS patients that were homozygous in two families and compound heterozygous in 12 families. In the 23 patients with nonsyndromic EVA, systematic thyroid evaluation found no abnormalities except for slightly increased thyroglobulin levels in two patients. SLC26A4 mutations were identified in 9/23 (39%). Mutations were biallelic in two (compound heterozygous) and monoallelic in seven patients. CONCLUSION: The thyroid phenotype is widely variable in PS. SLC26A4 mutation screening is needed in patients exhibiting PS or nonsyndromic EVA. PS is associated with biallelic SLC26A4 mutations and nonsyndromic EVA with no, monoallelic, or biallelic SLC26A4 mutations. Systematic thyroid evaluation is recommended in patients with nonsyndromic EVA associated with one or two SLC26A4 mutations. We propose using a combination of three parameters to define and diagnose PS: (i) sensorineural deafness with bilateral EVA; (ii) thyroid abnormality comprising goiter and/or hypothyroidism and/or a positive PDT; (iii) biallelic SLC26A4 mutations.