Publications by authors named "Yves Alembik"

Article Synopsis
  • * In a study of 387,067 births in northeastern France from 1979 to 2007, 83 cases of RRD were found, resulting in a prevalence of 2.14 per 10,000 births, and 75.9% of these cases had additional congenital anomalies.
  • * The co-occurring anomalies included chromosomal disorders, syndromic conditions like VACTERL association, and multiple congenital anomalies (MCA), affecting various systems such as musculoskeletal, cardiovascular, urinary, and orofacial; a multidisciplinary approach is advised for managing such cases.
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  • The study analyzes data from two groups of individuals with DDX3X variations, one from physicians (48 individuals) and the other from caregivers (44 individuals).
  • The results reveal shared symptoms between the two groups, including previously unreported early childhood issues like feeding difficulties and delayed developmental milestones.
  • The discussion emphasizes that both datasets complement each other, highlighting the importance of addressing symptoms such as ADHD, anxiety, and sleep disturbances in affected individuals.
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Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007.

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Associated congenital anomalies may be observed in cases with achondroplasia. The prevalence reported in the literature and the types of co-occurring congenital anomalies are variable between the reported studies. The aim of this study was to establish the prevalence and to describe the associated anomalies in cases with achondroplasia.

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Oral clefts (OCs) are frequently co-occurring with other non-OC congenital anomalies. The types and the prevalence of anomalies co-occurring with OCs vary in the reported studies. The aims of this report were to study the types and the prevalence of the anomalies co-occurring with OCs in a well-defined population.

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Background: High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD).

Methods: This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous coding variants, occurring de novo for all those whose transmission could have been verified (26/28).

Results: A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues.

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Purpose: Haploinsufficiency of PSMD12 has been reported in individuals with neurodevelopmental phenotypes, including developmental delay/intellectual disability (DD/ID), facial dysmorphism, and congenital malformations, defined as Stankiewicz-Isidor syndrome (STISS). Investigations showed that pathogenic variants in PSMD12 perturb intracellular protein homeostasis. Our objective was to further explore the clinical and molecular phenotypic spectrum of STISS.

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  • Complete gene deletion occurs in 5-10% of neurofibromatosis type 1 (NF1) patients, with a significant representation (4%) observed in a large French cohort of 3,479 cases.
  • A comprehensive clinical evaluation revealed that 93% of patients with gene deletion met the NIH criteria for NF1, showing a higher incidence of symptoms like café-au-lait spots, neurofibromas, and learning disabilities.
  • Compared to typical NF1 cases, the -deleted cohort displayed more severe symptoms, including a higher percentage of spinal neurofibromas, dysmorphism, and various systemic abnormalities.
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Dysregulated transforming growth factor TGF-β signaling underlies the pathogenesis of genetic disorders affecting the connective tissue such as Loeys-Dietz syndrome. Here, we report 12 individuals with bi-allelic loss-of-function variants in IPO8 who presented with a syndromic association characterized by cardio-vascular anomalies, joint hyperlaxity, and various degree of dysmorphic features and developmental delay as well as immune dysregulation; the individuals were from nine unrelated families. Importin 8 belongs to the karyopherin family of nuclear transport receptors and was previously shown to mediate TGF-β-dependent SMADs trafficking to the nucleus in vitro.

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The pathogenesis of omphalocele and gastroschisis is not obvious. Their etiology is disputed. The prevalence and the types of anomalies co-occurring with omphalocele and gastroschisis are variable in the different series published.

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  • The study investigates the clinical and genetic characteristics of β-galactosidase deficiency, focusing on two conditions: GM1-gangliosidosis and mucopolysaccharidosis IVB (MPSIVB).
  • Researchers analyzed data from 52 patients, finding a range of clinical symptoms in GM1-gangliosidosis from severe prenatal forms to adult onset.
  • The study identified numerous genetic variants, including 18 new ones, linking specific variants to distinct types of these disorders, ultimately aiming to improve patient classification and management.
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Post-mortem genetic analyses may help to elucidate the cause of cardiac death. The added value is however unclear when a cardiac disease is already suspected or affirmed. Our aim was to study the feasibility and medical impact of post-mortem genetic analyses in suspected cardiomyopathy.

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Purpose: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD.

Methods: We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients.

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Children with Down syndrome (DS) suffer from recurrent respiratory infections, which represent the leading cause of mortality during childhood. This susceptibility to infections is usually considered multifactorial and related to both impaired immune function and non-immunological factors. Infections are also one of the top causes of death in DS at adulthood.

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Thrombocytopenia-absent radius (TAR) syndrome is characterized by radial defect and neonatal thrombocytopenia. It is caused by biallelic variants of RBM8A gene (1q21.1) with the association of a null allele and a hypomorphic noncoding variant.

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Background: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level.

Methods: 7 patients with newly identified mutations in (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions.

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Article Synopsis
  • Lamb-Shaffer syndrome (LAMSHF) is a rare neurodevelopmental disorder linked to genetic changes in the SOX5 gene, primarily through microdeletions, affecting brain development and function.
  • The study analyzed data from 41 new patients with different SOX5 alterations to better understand the genetic variations and their impact on clinical symptoms.
  • Findings revealed that while most genetic changes disrupt SOX5's ability to bind DNA, leading to varying degrees of intellectual disability and language delays, the severity of symptoms doesn't strongly correlate with specific genetic alterations.
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Amelogenesis imperfecta (AI) is a heterogeneous group of rare inherited diseases presenting with enamel defects. More than 30 genes have been reported to be involved in syndromic or non-syndromic AI and new genes are continuously discovered (Smith et al., 2017).

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Background: Down syndrome (DS) is the most common form of viable chromosomal abnormality. DS is associated with recurrent infections, auto-immunity and malignancies in children. Little is known about immunity and infections in DS at adulthood.

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Anorectal anomalies (ARA) are common congenital anomalies. The etiology of ARA is unclear and its pathogenesis is controversial. Cases with ARA often have other non-ARA-associated congenital anomalies.

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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control neuronal excitability and their dysfunction has been linked to epileptogenesis but few individuals with neurological disorders related to variants altering HCN channels have been reported so far. In 2014, we described five individuals with epileptic encephalopathy due to de novo HCN1 variants. To delineate HCN1-related disorders and investigate genotype-phenotype correlations further, we assembled a cohort of 33 unpublished patients with novel pathogenic or likely pathogenic variants: 19 probands carrying 14 different de novo mutations and four families with dominantly inherited variants segregating with epilepsy in 14 individuals, but not penetrant in six additional individuals.

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Deletions at chromosome 2p25.3 are associated with a syndrome consisting of intellectual disability and obesity. The smallest region of overlap for deletions at 2p25.

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Esophageal atresia (EA) is a common type of congenital anomaly. The etiology of esophageal atresia is unclear and its pathogenesis is controversial. Infants with esophageal atresia often have other non-EA associated congenital anomalies.

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Noonan syndrome is a heterogeneous autosomal dominant disorder caused by mutations in at least eight genes involved in the RAS/MAPK signaling pathway. Recently, RIT1 (Ras-like without CAAX 1) has been shown to be involved in the pathogenesis of some patients. We report a series of 44 patients from 30 pedigrees (including nine multiplex families) with mutations in RIT1.

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