Evaluation of an Updated Gene Panel as a Diagnostic Tool for Both Male and Female Infertility.

In recent years, an increasing number of genes associated with male and female infertility have been identified. The genetics of infertility is no longer limited to the analysis of karyotypes or specific genes, and it is now possible to analyse several dozen infertility genes simultaneously. Here, we present the diagnostic activity over the past two years including 140 patients (63 women and 77 men).

WGS Revealed Novel Pathogenic Variants, Missed by WES, Causing Ciliary Structure and Function Defects.

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy that affects multiple organs, leading to retinitis pigmentosa, polydactyly, obesity, renal anomalies, cognitive impairment, and hypogonadism. Until now, biallelic pathogenic variants have been identified in at least 24 genes delineating the genetic heterogeneity of BBS. Among those, is a minor contributor to the mutation load and is one of the eight subunits forming the BBSome, a protein complex implied in protein trafficking within the cilia.

Case Report: A New Gain-of-Function Mutation of Identified in a Patient With Chronic Mucocutaneous Candidiasis and Rosacea-Like Demodicosis: An Emerging Association.

Purpose: Heterozygous missense mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis.

Methods: Genetic analysis targeted next-generation sequencing (NGS; NGS panel DIPAI v.

Evaluation of a Custom Design Gene Panel as a Diagnostic Tool for Human Non-Syndromic Infertility.

Infertility is a global healthcare problem, which affects men and women equally. With the advance of genome-wide analysis, an increasing list of human genes involved in infertility is now available. In order to evaluate the diagnostic interest to analyze these genes, we have designed a gene panel allowing the analysis of 51 genes involved in non-syndromic human infertility.

Protocol GenoDENT: Implementation of a New NGS Panel for Molecular Diagnosis of Genetic Disorders with Orodental Involvement.

Rare genetic disorders are often challenging to diagnose. Anomalies of tooth number, shape, size, mineralized tissue structure, eruption, and resorption may exist as isolated symptoms or diseases but are often part of the clinical synopsis of numerous syndromes (Bloch-Zupan A, Sedano H, Scully C. Dento/oro/craniofacial anomalies and genetics, 1st edn.

Assessment of a Targeted Gene Panel for Identification of Genes Associated With Movement Disorders.

Importance: Movement disorders are characterized by a marked genotypic and phenotypic heterogeneity, complicating diagnostic work in clinical practice and molecular diagnosis.

Objective: To develop and evaluate a targeted sequencing approach using a customized panel of genes involved in movement disorders.

Design, Setting And Participants: We selected 127 genes associated with movement disorders to create a customized enrichment in solution capture array.

Contribution of germline deleterious variants in the RAD51 paralogs to breast and ovarian cancers.

RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) have recently been involved in breast and ovarian cancer predisposition: RAD51B, RAD51C, and RAD51D in ovarian cancer, RAD51B and XRCC2 in breast cancer. The aim of this study was to estimate the contribution of deleterious variants in the five RAD51 paralogs to breast and ovarian cancers. The five RAD51 paralog genes were analyzed by next-generation sequencing technologies in germline DNA from 2649 consecutive patients diagnosed with breast and/or ovarian cancer.

Mosaicism and prenatal diagnosis options: insights from retinoblastoma.

In sporadic cases, a post-zygotic mutational event signifies a somatic mosaicism in the affected child only, which implies that these mutations affect only a portion of the body. Therefore siblings do not need follow-up. On the other hand, a pre-zygotic mutation transmitted by an unaffected mosaic parent implies recurrent risks in offspring.

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing.

Background: Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS).

Methods: Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes.

Genomic hallmarks of homologous recombination deficiency in invasive breast carcinomas.

Therapeutic strategies targeting Homologous Recombination Deficiency (HRD) in breast cancer requires patient stratification. The LST (Large-scale State Transitions) genomic signature previously validated for triple-negative breast carcinomas (TNBC) was evaluated as biomarker of HRD in luminal (hormone receptor positive) and HER2-overexpressing (HER2+) tumors. The LST genomic signature related to the number of large-scale chromosomal breakpoints in SNP-array tumor profile was applied to identify HRD in in-house and TCGA sets of breast tumors, in which the status of BRCA1/2 and other genes was also investigated.

Streamlined ion torrent PGM-based diagnostics: BRCA1 and BRCA2 genes as a model.

To meet challenges in terms of throughput and turnaround time, many diagnostic laboratories are shifting from Sanger sequencing to higher throughput next-generation sequencing (NGS) platforms. Bearing in mind that the performance and quality criteria expected from NGS in diagnostic or research settings are strikingly different, we have developed an Ion Torrent's PGM-based routine diagnostic procedure for BRCA1/2 sequencing. The procedure was first tested on a training set of 62 control samples, and then blindly validated on 77 samples in parallel with our routine technique.

Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.

The role of de novo mutations (DNMs) in common diseases remains largely unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of selection against de novo mutations are critical to understanding the genetic architecture of a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation of partial or complete genomes of families via resequencing.

De novo truncating mutation in Kinesin 17 associated with schizophrenia.

Background: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. It is thought to be due to a complex interplay between polygenic and various environmental risk factors, although recent reports on genomic copy number variations suggest that a fraction of the cases could result from variably penetrant de novo variants. The gene encoding the synaptic motor protein kinesin 17 (KIF17) involved in glutamatergic synapse is a candidate gene for SCZ.