Phillis Lakeman

Pathological disruption of CELF2 shuttling causes neuronal hyperactivity, learning deficits, and seizures

Michelle Hua, Mohamad-Reza Aghanoori, Melissa J. MacPherson, Yi Ren et autres

De novo heterozygous variants in CUGBP Elav-like family member 2 (CELF2) have recently been associated with a rare neurodevelopmental disorder, yet the mechanisms linking specific variants to distinct clinical phenotypes remain poorly understood. Here, we reported a cohort of 18 individuals and …

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Distinct sub-clusters of developmental disorder-associated variants in the switch II region of RAC1

Hebah O. Althebaiti, James Cooksedge, Martin J. Baker, M Smith et autres

RAC1 is a signal transducer essential for neurodevelopment. Missense variants in RAC1 cause heterogeneous neurodevelopmental disorders whose features include intellectual disability and developmental delay. Individuals with RAC1 variants are categorized by head circumference into microcephalic, normocephalic and macrocephalic groups. We previously described …

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Routine RNA-based analysis of potential splicing variants facilitates genomic diagnostics and reveals limitations of in silico prediction tools

Mark Drost, Jordy Dekker, Federico Ferraro, Esmee Kasteleijn et autres

DNA variants affecting pre-mRNA splicing are an important cause of genetic disorders and remain challenging to interpret without experimental data. Although variant classification guidelines recommend experimental characterization of variant splicing effects, the added value of routine diagnostic investigation of patient mRNA splicing …

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Genetic variants disrupting activity-dependent CELF2 shuttling cause neuronal hyperexcitability, learning deficits, and seizures

Michelle Hua, Mohamad‐Reza Aghanoori, Melissa J MacPherson, Yi Ren et autres

Abstract De novo heterozygous variants in the CELF2 gene have recently been associated with a rare neurodevelopmental disorder. However, the mechanisms linking specific variants to distinct clinical phenotypes remain poorly understood. Here, we report a new cohort of 14 individuals with de …

ca, fr, de, au, nl, us, gb, cn (code pays fourni par la source)

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

Niels Vos, Sadegheh Haghshenas, Liselot van der Laan, Perle K. M. Russel et autres

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 …

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Perceptions of reproductive healthcare providers regarding their involvement in offering expanded carrier screening in fertility clinics: a qualitative study

David J. Klein, Ivy van Dijke, Irene M. van Langen, Wybo Dondorp et autres

RESEARCH QUESTION: What are the main arguments of reproductive healthcare providers in favour or against their involvement in offering expanded carrier screening (ECS) for recessive disorders at fertility clinics in the Netherlands? DESIGN: Semi-structured interview study with 20 reproductive healthcare providers between …

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Medullary Sponge Kidney and Its Relationship with Primary Distal Renal Tubular Acidosis: Case Reports and a Comprehensive Genetics-First Approach

Gerrit van den Berg, Laura R. Claus, Bert van der Zwaag, Phillis Lakeman et autres

Medullary sponge kidney (MSK) is a description of radiographic features. However, the pathogenesis of MSK remains unclear. MSK is supposed to be the cause of secondary distal renal tubular acidosis (dRTA), although there are case reports suggesting that MSK is a complication …

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Developmental epileptic encephalopathy in DLG4 ‐related synaptopathy

Benedetta Kassabian, Amanda M. Levy, Elena Gardella, Ángel Aledo‐Serrano et autres

OBJECTIVE: The postsynaptic density protein of excitatory neurons PSD-95 is encoded by discs large MAGUK scaffold protein 4 (DLG4), de novo pathogenic variants of which lead to DLG4-related synaptopathy. The major clinical features are developmental delay, intellectual disability (ID), hypotonia, sleep disturbances, …

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Correction: Clinical findings and a DNA methylation signature in kindreds with alterations in ZNF711

Jiyong Wang, Aidin Foroutan, Ellen Richardson, Steven A. Skinner et autres

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Primary care professionals’ views on population-based expanded carrier screening: an online focus group study

Lieke M. van den Heuvel, Anke J. Woudstra, Sanne van der Hout, Suze Jans et autres

BACKGROUND: Population-based expanded carrier screening (ECS) involves screening for multiple recessive diseases offered to all couples considering a pregnancy or during pregnancy. Previous research indicates that in some countries primary care professionals are perceived as suitable providers for ECS. However, little is …

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Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

Katrine M. Johannesen, Yuanyuan Liu, Mahmoud Koko, Cathrine E. Gjerulfsen et autres

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Na(v)1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign …

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Views of patients and parents of children with genetic disorders on population‐based expanded carrier screening

Anke J. Woudstra, Lieke M. van den Heuvel, Elsbeth H. van Vliet‐Lachotzki, Wybo Dondorp et autres

OBJECTIVE: Faster and cheaper next generation sequencing technologies have enabled expansion of carrier screening for recessive disorders, potentially facilitating population-based implementation regardless of ancestry or family history. Little is known, however, about the attitudes regarding population-based carrier screening among families with genetic …

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