So far, variants in SHROOM4 have been associated with Stocco dos Santos syndrome, a neurodevelopmental disorder. Our report expands the clinical spectrum related to SHROOM4 variation: We identified single nucleotide variants and microdeletions in SHROOM4 in six individuals from four families, presenting with congenital anomalies of the urinary tract, the anorectum, the heart, and the […]
Latest articles
Homozygous truncating variant in MAN2A2 causes a novel congenital disorder of glycosylation with neurological involvement (Contributed by Dr. Sonal Mahajan)
Golgi enzymes involved in N-glycan processing are critical for brain development, deficiencies in many leads to congenital disorders of glycosylation (CDG) with multisystem effects, particularly affecting the brain. Our study presents the first report of pathogenic variants in MAN2A2, causing a novel autosomal recessive CDG with neurological involvement. We identified a multiplex consanguineous family with […]
Indepth characterization of a cohort of individuals with missense and loss-of-function variants disrupting FOXP2 (Contributed by Lottie Morison)
Heterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder; childhood apraxia of speech (CAS), yet few cases have been reported. We phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants. Speech disorders were prevalent into adulthood; with CAS the most common diagnosis. Cognition (average to mildly impaired) was incongruent […]
The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2 (Contributed by Sue Philpott)
Women with inherited BRCA1/2 gene alterations are at high risk of ovarian cancer, so usually opt for surgery to remove their ovaries and tubes. Many women delay surgery to complete families or avoid premature menopause. This study confirmed previous research showing that a 4-monthly blood test can detect ovarian cancer at earlier stages, resulting in […]
New insights into CC2D2A-related Joubert syndrome (Contributed by Madeleine Harion)
Joubert syndrome (JS) is a complex, genetic, neurological disorder which includes a specific cerebellum malformation. Multiple genes are implicated in this disease. It is known to be a severe disorder because it causes important neurodevelopmental disabilities and other complications such as low vision, kidney disorder and liver fibrosis. In our French cohort, JS patients caused […]
Reproductive choices and intrafamilial communication in neurogenetic diseases with different self-estimated severities. Pierron, et al. (Contributed by Lucie Pierron, Marcela Gargiulo and Alexandra Durr)
Autosomal dominant neurogenetic diseases are characterized by progressive motor and cognitive impairment without curative treatment. They present with variable disease severities and possible transmission to the offspring can be experienced as burdensome. All are accessible to assisted reproductive options. We conducted a survey to assess individual perception of disease severity, opinion on reproductive options and […]
GERMLINE MUTATIONS IN WNK2 COULD BE ASSOCIATED WITH SERRATED POLYPOSIS SYNDROME, Soares de Lima et al. (Contributed by Dr. Sergi Castellví-Bel)
Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. Our main aim was to identify the inherited genetic basis of this disease. We performed germline exome sequencing in 39 SPS patients from 16 families and sequenced specific genes in an independent cohort of 211 unrelated […]
The clinical, neuroimaging, and molecular characteristics of PPP2R5D related neurodevelopmental disorders: an expanded series with functional characterization and genotype-phenotype correlation (Contributed by Nora M Oyama, Pieter Vaneynde, Sara Reynhout, Emily C Pao, Andrew Timms, Xiao Fan, Kimberly Foss, Rita Derua, Veerle Janssens, Wendy K Chung and Ghayda M Mirzaa)
Genetics variants in the PPP2R5D gene have been identified to cause a neurodevelopmental disorder characterized by intellectual disabilities, autism spectrum disorder and epilepsy, among others features. Our study, describing 76 individuals, expands the known clinical and molecular spectrum of PPP2R5D related disorders. This allowed us to identify a correlation between groups of variants and their […]
Identifying the molecular drivers of ALS-implicated missense mutations (Contributed by Dr. David Ascher)
Genetic mutations have long been identified as contributors to ALS, however, their molecular-consequences have remained elusive. To address this, we analysed the effects of ALS missense mutations in SOD1, FUS and TDP-43 using in silico tools. FUS and TDP-43 mutations affected disordered regions associated with phase separation and aggregation, while SOD1 mutations destabilized the homodimer, […]
Prospective validation of the BOADICEA multifactorial breast cancer risk prediction model in a large prospective cohort study (Contributed by Xin Yang)
BOADICEA is a multifactorial breast cancer risk model for predicting the future risk of developing breast cancer on the basis of the combined effects of cancer family history, lifestyle, hormonal and reproductive risk factors, mammographic density, polygenic risk score and rare pathogenic variants in all eight established breast cancer susceptibility genes. Here, Yang et al […]