genomic rearrangements in a 391 French bilateral periventricular nodular heterotopia cohort: prevalence and phenotypic correlations.

Background: loss of function manifests across a broad spectrum of phenotypes, ranging from severe prenatal onset to asymptomatic cases. Bilateral periventricular nodular heterotopia (BPNH) consistently occurs in affected individuals. This retrospective study involving French patients with BPNH evaluates the prevalence of gene dosage anomalies and investigates genotype-phenotype correlations in a large cohort of French patients with BPNH.

Deletion in 2q35 excluding the IHH gene leads to fetal severe limb anomalies and suggests a disruption of chromatin architecture.

The organization of mammalian genomes into sub-megabase sized Topologically Associated Domains (TADs) has recently been revealed by techniques derived from Chromosome Conformation Capture (3 C), such as High Chromosome Contact map (Hi-C). Disruption of this organization by structural variations can lead to ectopic interactions between enhancers and promoters, and to alteration of genes expression patterns. This mechanism has already been described as the main pathophysiological mechanism in several syndromes with congenital malformations.

Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.

Otopalatodigital spectrum disorders (OPDSD) constitute a group of dominant X-linked osteochondrodysplasias including four syndromes: otopalatodigital syndromes type 1 and type 2 (OPD1 and OPD2), frontometaphyseal dysplasia, and Melnick-Needles syndrome. These syndromes variably associate specific facial and extremities features, hearing loss, cleft palate, skeletal dysplasia and several malformations, and show important clinical overlap over the different entities. FLNA gain-of-function mutations were identified in these conditions.

New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Objective: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in the SACS gene. SACS encodes sacsin, a protein whose function remains unknown, despite the description of numerous protein domains and the recent focus on its potential role in the regulation of mitochondrial physiology. This study aimed to identify new mutations in a large population of ataxic patients and to functionally analyze their cellular effects in the mitochondrial compartment.

New candidate loci identified by array-CGH in a cohort of 100 children presenting with syndromic obesity.

Syndromic obesity is defined by the association of obesity with one or more feature(s) including developmental delay, dysmorphic traits, and/or congenital malformations. Over 25 syndromic forms of obesity have been identified. However, most cases remain of unknown etiology.

Prenatal diagnosis using array-CGH: a French experience.

Array-CGH or Chromosomal Microarray Analysis (CMA) is increasingly used in prenatal diagnosis throughout the world. However, routine practices are very different among centers and countries, regarding CMA indications, design and resolution of microarrays, notification and interpretation of Copy Number Alterations (CNA). We present our data and experience from our Fetal Medicine Center on 224 prospective prenatal diagnoses.

Dysmorphic features in subtelomeric 20p13 deletion excluding JAG1: a recognizable microdeletion phenotype?

We report a 19 year-old patient carrying a terminal 20p microdeletion. She displayed clinical features resembling those of two other previously described patients. We suggest that a specific phenotype can be associated with this chromosomal anomaly.

1.5 Mb microdeletion in 15q24 in a patient with mild OAVS phenotype.

We report on a boy presenting with features of OAVS (Oculoauriculovertebral spectrum) and carrying a 1.5 Mb microdeletion in 15q24.1q24.

Array-CGH analysis of a cohort of 86 patients with oculoauriculovertebral spectrum.

Oculoauriculovertebral spectrum (OAVS) is a clinically and genetically heterogeneous congenital disorder. We performed high density oligonucleotide array-CGH on 86 OAVS patients and identified in 11 patients 12 novel genomic rearrangements (4 deletions and 8 duplications) ranging in size from 2.7 kb to 2.