Background: Rhabdoid tumors (RT) are aggressive, rare tumors predominantly affecting young children, characterized by biallelic SMARCB1 gene inactivation. While most SMARCB1 alterations are acquired de novo, a third of cases exhibit germline alterations, defining Rhabdoid Tumors Predisposition Syndrome. With the increased sensitivity of next-generation sequencing (NGS), mosaicisms in genes linked to genetic diseases are more detectable.
View Article and Find Full Text PDFIn paediatric oncology, genomics raises new ethical, legal and psychological issues, as somatic and constitutional situations intersect throughout the care pathway. The discovery of potential predisposition in this context is sometimes carried out outside the usual framework. This article focuses on the views of children, adolescents, and young adults (AYA) with cancer and their parents about their experience with genomic testing.
View Article and Find Full Text PDFBackground: pathogenic variants (PV) have been recently identified as the most frequent variants predisposing to Sonic Hedgehog (SHH) medulloblastomas (MB); however, guidelines are still lacking for genetic counseling in this new syndrome.
Methods: We retrospectively reviewed clinical and genetic data of a French series of 29 -mutated MB.
Results: All patients developed SHH-MB, with a biallelic inactivation of found in 24 tumors.
Objective: New genome sequencing techniques allow new approaches in medical genetics, in particular by facilitating the diagnosis of genetic diseases. However, their use also leads to unsolicited genetic findings being uncovered. This type of discovery raises ethical, legal and psychological considerations.
View Article and Find Full Text PDFDeficient anterior pituitary with common variable immune deficiency (DAVID) syndrome is a rare condition characterized by adrenocorticotropic hormone (ACTH) deficiency and primary hypogammaglobulinemia. It is due to heterozygous mutations of the nuclear factor kappa-B subunit 2 (NFKB2) gene. Only a few isolated cases have been reported since its first description by our team.
View Article and Find Full Text PDFThe neuronal SNARE complex drives synaptic vesicle exocytosis. Therefore, one of its core proteins syntaxin 1A (STX1A) has long been suspected to play a role in neurodevelopmental disorders. We assembled eight individuals harboring ultra rare variants in STX1A who present with a spectrum of intellectual disability, autism and epilepsy.
View Article and Find Full Text PDFBackground: Pathogenic variants in MYH11 are associated with either heritable thoracic aortic aneurysm and dissection (HTAAD), patent ductus arteriosus (PDA) syndrome, or megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS).
Methods And Results: We report a family referred for molecular diagnosis with HTAAD/PDA phenotype in which we found a variant at a non-conserved position of the 5' donor splice site of intron 32 of MYH11 potentially altering splicing (NM_002474.3:c.
Purpose: The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood.
Methods: Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed.
Results: Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified.
Nucleotide excision repair associated diseases comprise overlapping phenotypes and a wide range of outcomes. The early stages still remain under-investigated and underdiagnosed, even although an early recognition of the first symptoms is of utmost importance for appropriate care and genetic counseling. We systematically collected clinical and molecular data from the literature and from newly diagnosed NER patients with neurological impairment, presenting clinical symptoms before the age of 12 months, including foetal cases.
View Article and Find Full Text PDFBackground: Pathogenic SMAD3 variants are responsible for a cardiovascular phenotype, mainly thoracic aortic aneurysms and dissections. Precocious identification of the vascular risk such as aortic dilatation in mutated patients has a major impact in terms of management, particularly to avoid dissection and sudden death. These vascular damages are classically associated with premature osteoarthritis and skeletal abnormalities.
View Article and Find Full Text PDFNext-generation sequencing techniques enable unsolicited findings to be detected. This discovery raises ethical questions concerning the return of these findings. Our study aimed to highlight the views of the general public, patients under supervision and health professionals concerning the acceptability of disclosing unsolicited results to patients.
View Article and Find Full Text PDFAtaxia-telangiectasia (A-T) is a recessive disorder caused by biallelic pathogenic variants of ataxia-telangiectasia mutated (ATM). This disease is characterized by progressive ataxia, telangiectasia, immune deficiency, predisposition to malignancies, and radiosensitivity. However, hypomorphic variants may be discovered associated with very atypical phenotypes, raising the importance of evaluating their pathogenic effects.
View Article and Find Full Text PDFObjective: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers.
Methods: We reviewed the phenotype of patients carrying a mutation in the SCN8A gene, among a multicentric cohort of 638 patients prospectively followed by several pediatric neurologists. We focused on the way clinicians made the diagnosis of epileptic encephalopathy, the very first symptoms, electroencephalography (EEG) findings, and seizure types.