Immunofluorescence analysis in a FGF9-D195N mouse model: XY Fgf9^D195N/− mice show partial gonadal sex reversal, expressing the meiotic germ cell marker γH2AX (b) and the ovarian somatic cell marker FOXL2 (d). XY Fgf9^+/− mice were used as controls (a, c). AMH is a marker of testicular Sertoli cells. Scale bars 100 μm.

Reanalysis of 287 nondiagnostic clinical exomes from Ontario, Canada revealed few missed diagnoses by the clinical laboratories and the incremental gain from reanalysis of clinically-relevant genes is modest. The highest yield came from translational research methods to validate novel disease-gene associations.

CST6 mutations cause dry skin without hypotrichosis.

Biallelic variants in SPATA20 resulted in acephalic spermatozoa syndrome in humans, characterized by disrupted assembling of head-tail coupling apparatus (HTCA) and aberrant sperm tail.

Targeted sequencing and Sanger sequencing identified NDP and TSPAN12 variants from FEVR patients. The four missense variants in TSPAN12 cause defective membrane trafficking ability, leading to decreased Norrin/β-catenin signaling. The Cys119Tyr and His42Asn variants in NDP cause compromised Norrin/β-catenin signaling by disrupting interactions with FZD4 and LRP5, respectively, which can be enhanced by over-expression of TSPAN12.

French healthcare professionals have to face with challenging report and genetic counseling regarding PIEV CNVs. Our study consists in purposing them a survey about their opinions and practices of which results highlight that multidisciplinary concertation has to be the main basis for French recommendations.

We report a novel heterozygous missense variant in AFF3 (c.2915G > C: p.Arg972Pro) associated with isolated syndactyly. Our zebrafish assay suggested that the variant is loss-of-function. Our results establish the first association of AFF3 with isolated syndactyly and expand the clinical spectrum associated with variants in AFF3.

In this study we report three new unrelated patients from Middle-East consanguineous families carrying the previously described NM_004722.4(AP4M1):c.1012C〉T homozygous nonsense variant. We describe their phenotype, and provide evidence that the subjects carrying this variant originate from a common ancestor.

We identified eight potential variants in five genes (MSH4, HFM1, SYCE1, FSHR and C14orf39) from six independent families in infertile females characterized by ovarian dysfunction with exome sequencing. The missense variants in FSHR were conserved across species. And the splice-site variants in MSH4 and SYCE1 affected canonical splicing isoforms, leading to missing protein domains or premature termination.

We report compound heterozygous variants in a bifunctional aminoacyl-tRNA synthetase, EPRS1, in a 4-year-old female patient presenting with psychomotor developmental delay, seizures and deafness. Functional studies of these two missense mutations support major defects in enzymatic function in vitro and contributed to confirmation of the diagnosis.

We first identify a novel ZNF148 heterozygous truncating variant c.1818dupC (p.Lys607Glnfs*11) in a patient with distinct phenotypes of ASD and ADHD. This variation produces a ZNF148 truncated protein with a deletion of the C-terminal activation domain and may destabilize the protein by affecting the transcriptional activation function.

The update of the review on the effects of switching from agalsidase beta to alfa showed, in comparison to the previous review, an increased number of clinical events, a significant loss of renal function, and an increase in lyso Gb-3 levels, underscoring the importance of dose in the treatment of FD.

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