Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140.

Rationale & Objective: Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.

Study Design: Case series.

Expectations, needs and mid-term outcomes in people accessing to secondary findings from ES: 1st French mixed study (FIND Study).

Generation and subsequently accessibility of secondary findings (SF) in diagnostic practice is a subject of debate around the world and particularly in Europe. The French FIND study has been set up to assess patient/parent expectations regarding SF from exome sequencing (ES) and to collect their real-life experience until 1 year after the delivery of results. 340 patients who had ES for undiagnosed developmental disorders were included in this multicenter mixed study (quantitative N = 340; qualitative N = 26).

The detection of a strong episignature for Chung-Jansen syndrome, partially overlapping with Börjeson-Forssman-Lehmann and White-Kernohan syndromes.

Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It is caused by pathogenic variants in the PHIP gene that encodes for the Pleckstrin homology domain-interacting protein, which is part of an epigenetic modifier protein complex. Therefore, we hypothesized that PHIP haploinsufficiency may impact genome-wide DNA methylation (DNAm).

Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene.

Achaete-Scute Family basic-helix-loop-helix (bHLH) Transcription Factor 1 (ASCL1) is a proneural transcription factor involved in neuron development in the central and peripheral nervous system. While initially suspected to contribute to congenital central hypoventilation syndrome-1 (CCHS) with or without Hirschsprung disease (HSCR) in three individuals, its implication was ruled out by the presence, in one of the individuals, of a Paired-like homeobox 2B (PHOX2B) heterozygous polyalanine expansion variant, known to cause CCHS. We report two additional unrelated individuals sharing the same sporadic ASCL1 p.

Neurodevelopmental and other phenotypes recurrently associated with heterozygous BAZ2B loss-of-function variants.

The bromodomain adjacent to zinc finger 2B (BAZ2B) gene encodes a chromatin remodeling protein that has been shown to perform a variety of regulatory functions. It has been proposed that loss of BAZ2B function is associated with neurodevelopmental phenotypes, and some recurrent structural birth defects and dysmorphic features have been documented among individuals carrying heterozygous loss-of-function BAZ2B variants. However, additional evidence is needed to confirm that these phenotypes are attributable to BAZ2B deficiency.

Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition.

Pathogenic variants in ATP-dependent chromatin remodeling proteins are a recurrent cause of neurodevelopmental disorders (NDDs). The NURF complex consists of BPTF and either the SNF2H () or SNF2L () ISWI-chromatin remodeling enzyme. Pathogenic variants in and were previously implicated in NDDs.

Patient satisfaction, experience and preferences in the implementation of genetics teleconsultations in the North-eastern region of France.

Introduction: In France, few centres per region offer genetics consultations. Consequently, each centre covers a large area, often requiring patients to take a day off to travel long distances. In certain situations, genetic counselling in particular, a physical exam is not required.

Advancing precision oncology through systematic germline and tumor genetic analysis: The oncogenetic point of view on findings from a prospective multicenter clinical trial of 666 patients.

Introduction: With the emergence of targeted therapies, there is a need to accurately identify more tumor biomarkers. The EXOMA trial was designed to offer tumor and germline exome sequencing (ES) to patients with solid malignant tumors and facing therapeutic failure. As hereditary cancer predispositions could be identified, with genetic counseling and health management implications, a genetic consultation was systematically established.

Association and performance of polygenic risk scores for breast cancer among French women presenting or not a familial predisposition to the disease.

Background: Three partially overlapping breast cancer polygenic risk scores (PRS) comprising 77, 179 and 313 SNPs have been proposed for European-ancestry women by the Breast Cancer Association Consortium (BCAC) for improving risk prediction in the general population. However, the effect of these SNPs may vary from one country to another and within a country because of other factors.

Objective: To assess their associated risk and predictive performance in French women from (1) the CECILE population-based case-control study, (2) BRCA1 or BRCA2 (BRCA1/2) pathogenic variant (PV) carriers from the GEMO study, and (3) familial breast cancer cases with no BRCA1/2 PV and unrelated controls from the GENESIS study.

Asymmetric crying facies in an elderly, when a facial asymmetry is not a facial paralysis but a marker of possible congenital malformations: case report and review of the literature.

Background: Facial asymmetry when crying at birth (then called asymmetric crying facies or ACF) or when smiling or speaking loudly in adulthood is the consequence of the agenesis or hypoplasia of the muscle of one of the labial commissures. This developmental disorder of complex mechanism is well known by pediatricians to be a warning sign for underlying developmental disorders of variable severity.

Case Report: An 80-year-old man with medical history of renal agenesis was hospitalized for a transient motor deficit of the right face and arm revealing a lacunar stroke.

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers.

The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation.