Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis.

BACKGROUND: Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool. METHODS: We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3). RESULTS: Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel. CONCLUSIONS: Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

[Screening for sensory defects in infants: the application of recommendations by GPs in the Maine-et-Loire region]. / Dépistage des troubles visuels et auditifs chez l'enfant. Application des recommandations chez les médecins généralistes du Maine-et-Loire.

Early detection of sight problems and hearing difficulties in babies facilitates better management of treatment by doctors who take care of them. This role is mainly played by general practitioners who conduct obligatory post-natal examinations at 9 and 24 months. A survey was carried out via questionnaire sent to all of the general practitioners from a French department in order to discover more about their daily clinical practice regarding the detection of sensory defects. Twenty nine per cent (n = 321) of them answered the survey. We observe that the clinical examination is not systematic, and that it is mainly carried out when babies are 4, 9 and 24 months old or upon the parents' request. Although clinical symptoms are for the most part well-known by general practitioners, signs of risk factors which might be present are not thoroughly examined. The clinical examination remains general with a broad overview by checking of the main visual reflexes, but with only a superficial examination of the strabismus and amblyopia. The hearing examination is mainly carried out with the use of voice or hand clapping, although two thirds of them have tools for gauging at their disposal. The minimum age required for treating eye trouble and hearing difficulties is not well known by practitioners and the ignorance of that fact can delay the implementation of a good care plan. The new health and medical record system should enable practitioners to more accurately detect sensory disorders in babies. Better dissemination of information and treatment option recommendations is needed.