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.

[Unilateral partial deferential agenesia and CFTR gene composite heterozygoty (deltaF508/V938G)].

This is a case report of a thirty-year-old-man consulting for a primary infertility that was diagnosed four years ago. Andrologic exam was normal. Two spermograms found normal spermatic parameters.

[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].

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.

GUG is an efficient initiation codon to translate the human mitochondrial ATP6 gene.

A maternally inherited and practically homoplasmic mitochondrial (mtDNA) mutation, 8527A>G, changing the initiation codon AUG into GUG, normally coding for a valine, was observed in the ATP6 gene encoding the ATPase subunit a. No alternate Met codon could replace the normal translational initiator. The patient harboring this mutation exhibited clinical symptoms suggesting a mitochondrial disease but his mother who carried the same mtDNA mutation was healthy.

Human airway mucin glycosylation: a combinatory of carbohydrate determinants which vary in cystic fibrosis.

Human airway mucins represent a very broad family of polydisperse high molecular mass glycoproteins, which are part of the airway innate immunity. Apomucins, which correspond to their peptide part, are encoded by at least 6 different mucin genes (MUC1, MUC2, MUC4, MUC5B, MUC5AC and MUC7). The expression of some of these genes (at least MUC2 and MUC5AC) is induced by bacterial products, tobacco smoke and different cytokines.

Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for mutations associated with Best's vitelliform macular dystrophy.

We identified three novel VMD2 mutations in patients with Best's macular dystrophy. DHPLC analysis of the 11 VMD2 exons revealed abnormal profiles in exon 8. Direct sequencing showed that these abnormal profiles were due to monoallelic transitions and transversions.

[Pendred's syndrome. Current features].

Introduction Pendred's syndrome is a recessive autosomal disease, traditionally defined as the association of deaf-mutism, goiter and dysfunctional iodide organization revealed by the perchlorate discharge test. It represents 4 to 10% of the causes of congenital hypoacusis. Although described more than a 100 years ago, the association of thyroid and cochleo-vestibular damage remained unclear for many years.

Identification of novel VMD2 gene mutations in patients with best vitelliform macular dystrophy.

ABSTRACT We report five novel VMD2 mutations in Best's macular dystrophy patients (S16F, I73N, R92H, V235L, and N296S). An SSCP analysis of the VMD2 11 exons revealed electrophoretic mobility shifts exclusively in exons 2, 3, 4, 6 and 8. Direct sequencing indicated that these shifts are caused by mono-allelic transition in exons 2, 4, 6, 8 and transversion in exons 3 and 6.

Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France.

We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 19 laboratories in France. We have analyzed 7, 420 CF alleles, demonstrating a total of 310 different mutations including 24 not reported previously, accounting for 93.56% of CF genes.

The sialylation of bronchial mucins secreted by patients suffering from cystic fibrosis or from chronic bronchitis is related to the severity of airway infection.

Bronchial mucins were purified from the sputum of 14 patients suffering from cystic fibrosis and 24 patients suffering from chronic bronchitis, using two CsBr density-gradient centrifugations. The presence of DNA in each secretion was used as an index to estimate the severity of infection and allowed to subdivide the mucins into four groups corresponding to infected or noninfected patients with cystic fibrosis, and to infected or noninfected patients with chronic bronchitis. All infected patients suffering from cystic fibrosis were colonized by Pseudomonas aeruginosa.

Length variations of the poly(T) tract at the exon 3 splice acceptor site of the choroideremia gene.

By using the single strand conformational analysis to search for point mutations in the choroideremia gene, we have identified an intronic polymorphism within the intron 2 of the CHM gene. We have studied the frequency of this polymorphism in the population from South of France.

[Correlation of genitourinary abnormalities, spermiogram and CFTR genotype in patients with bilateral agenesis of the vas deferens].

Objectives: To evaluate the frequency of urogenital ultrasound and spermatic abnormalities in patients with bilateral vas deferens agenesis according to the presence or absence of CFTR gene mutation.

Methods: In 41 patients with bilateral vas deferens agenesis confirmed by surgical exploration between 1988 and 1997, renal and seminal vesicle anomalies were investigated by ultrasonography. Spermatic parameters (pH, fructose and ejaculate volume) were also studied, together with sweat chloride assay and PCR of mutations on exons 3, 4, 7, 9, 10, 11, 13, 14b, 17b, 19, 20 and 21 of the CFTR gene.

Altered rep-1 expression due to substitution at position +3 of the IVS13 splice-donor site of the choroideremia (CHM) gene.

Purpose: To characterize the effect on mRNA splicing of a yet undescribed mutation located in intron 13 splice-donor sequence (IVS13 + 3A --> C) in the Rab-Escort-protein 1 gene of a patient with choroideremia.

Methods: The base substitution was firstly detected by the Single Strand conformation analysis from genomic DNA. A REP-1 cDNA region encompassing exons 10-14 was then specifically amplified from lymphocytes-derived mRNA.

Correlation between genito-urinary anomalies, semen analysis and CFTR genotype in patients with congenital bilateral absence of the vas deferens.

Objective: To evaluate the incidence of renal and seminal vesicle (SV) abnormalities, and the presence or absence of CFTR gene mutations, in a cohort of patients referred for congenital bilateral absence of the vas deferens (CBAVD).

Patients And Method: Forty-one patients with CBAVD, confirmed by surgical exploration, were evaluated by ultrasonography for renal and SV anomalies. Semen variables (pH, fructose level and ejaculate volume), sweat chloride levels and mutations of the 3, 4, 7, 9, 10, 11, 13, 14b, 17b, 19, 20 and 21 exons of the CFTR gene were determined.

Congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis transmembrane regulator (CFTR): correlation between genotype and phenotype.

To assess better the link between congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis (CF), we compared sweat chloride values, analysis of the CFTR intron 8 poly(T) tract length and analysis of 10 exons in a population of 38 patients with CBAVD. The data indicate that this population can be divided into three groups of patients. In the first group of 15 patients with abnormal sweat chloride (> 60 mmol/l), the frequency of CF mutations is high.

Genetic analysis of new French X-linked juvenile retinoschisis kindreds using microsatellite markers closely linked to the RS locus: further narrowing of the RS candidate region.

The gene involved in juvenile retinoschisis (RS) has previously been localized, by genetic linkage analyses, to Xp22.1-p22.2, between DXS274 and DXS43/DXS207; it is closely linked to the latter markers.

Genotypes of cytochrome P450 and clinical response to clomipramine in patients with major depression.

The genetic cytochrome P450 polymorphism is reported in factors affecting the individual response to drugs. The interindividual variation at steady-state levels or also in elimination of drugs, finds an explanation in genetic differences in the metabolism. In particular, activities of the P450-IID6 isoenzyme are related to the sparteine/debrisoquine oxidation polymorphism.