Publications by authors named "Malan V"
Purpose: CTLA4 deficiency is an inborn error of immunity (IEI) due to heterozygosity for germline loss-of-function variants of the CTLA4 gene located on chromosome 2q33.2. CTLA4 deficiency underlies pleiotropic immune and lymphoproliferation-mediated features with incomplete penetrance.
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- Cerebellar atrophy and hypoplasia, often detected through MRI in children with ataxia and developmental issues, are linked to leukodystrophies, which can affect brain myelin.
- A recent study highlights two cases involving variants in the LSM7 gene: one child with a confirmed diagnosis and another with a presumed variant, suggesting LSM7's critical role in these conditions.
- Our findings expand this understanding by presenting a new patient with similar symptoms and genetic variants in LSM7, reinforcing its association with neurodevelopmental disorders involving leukodystrophy and cerebellar atrophy.
Article Synopsis
- * The study presented data on five new patients and analyzed previous reports, identifying critical gene regions within 20q that may be responsible for observed syndromic features, which include two main regions containing disease-related genes.
- * Researchers suggest that GDF5 is the main gene associated with the syndrome linked to 20q11.2 deletions, while TOP1 may play a role in the second critical region at 20q12, noting the need for further
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- Duplications of the 3q29 chromosomal region are rare genetic variations linked to diverse neurodevelopmental disorders, often causing learning disabilities and neuropsychiatric issues.
- A study involving 31 families revealed different sizes of 3q29 duplications: 14 recurrent, 8 overlapping, and 9 smaller ones, with some patients showing additional genetic factors influencing their conditions.
- Most patients exhibited mild neurodevelopmental disorders, with many duplications being inherited and associated with low rates of intellectual disabilities, suggesting that severe cases might require more detailed genetic examination.
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- The case study reports a rare occurrence of uniparental disomy associated with a supernumerary marker chromosome 6 in a patient, leading to partial trisomy 6p12.3p11.1.
- The patient experienced growth retardation, macroglossia, developmental delays, and diabetes conditions likely linked to the genetic variations.
- More research and clinical examinations are required to understand the implications of partial trisomy 6p for effective genetic counseling and to consider uniparental disomy in early diagnoses involving marker chromosomes.
Bi-allelic variants in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene have been involved in early-onset encephalopathies classified as pontocerebellar hypoplasia (PCH) type 6 and in epileptic encephalopathy. A variant (NM_020320.3:c.
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- - The study focused on collecting and analyzing cases of fetuses with 7q11.23 copy number variations (CNVs), specifically Williams-Beuren syndrome (WBS) and 7q11.23 duplication, to enhance understanding of their prenatal features.
- - Researchers gathered clinical and ultrasound data from 40 fetuses with WBS, finding that common issues included intra-uterine growth retardation (IUGR), cardiovascular defects, and other notable signs.
- - The findings confirm that 7q11.23 CNVs lead to a variety of prenatal presentations, with IUGR and cardiovascular issues being the most prevalent, aiming to help identify distinctive signs in affected fetuses.
Background: Hereditary lymphedema 1 is a rare congenital condition, characterized by the development of chronic swelling in body parts. It is highly variable in expression and age of onset with different presentations: from feet edema to hydrops fetalis. This affection is genetically heterogeneous with autosomal dominant inheritance and incomplete penetrance due to a mutation in the FLT4 gene in most cases.
View Article and Find Full Text PDFDevelopmental abnormalities provide a unique opportunity to seek for the molecular mechanisms underlying human organogenesis. Esophageal development remains incompletely understood and elucidating causes for esophageal atresia (EA) in humans would contribute to achieve a better comprehension. Prenatal detection, syndromic classification, molecular diagnosis, and prognostic factors in EA are challenging.
View Article and Find Full Text PDFBackground: Ellis-Van Creveld (EVC) syndrome is one of the entities belonging to the skeletal ciliopathies short rib-polydactyly subgroup. Major signs are ectodermal dysplasia, chondrodysplasia, polydactyly and congenital cardiopathy, with a high degree of variability in phenotypes ranging from lethal to mild clinical presentations. The and genes are the major genes causative of EVC syndrome.
View Article and Find Full Text PDFHighly identical segmental duplications (SDs) account for over 5% of the human genome and are enriched in the short arm of the chromosome 16. These SDs are susceptibility factors for recurrent chromosomal rearrangements mediated by non-allelic homologous recombination (NAHR). Chromosomal microarray analysis (CMA) has been widely used as the first-tier test for individuals with developmental disabilities and/or congenital anomalies and several genomic disorders involving the 16p-arm have been identified with this technique.
View Article and Find Full Text PDFBackground And Purpose: Prognosis of isolated short corpus callosum is challenging. Our aim was to assess whether fetal DTI tractography can distinguish callosal dysplasia from variants of normal callosal development in fetuses with an isolated short corpus callosum.
Materials And Methods: This was a retrospective study of 37 cases referred for fetal DTI at 30.
Purpose: To correlate the degree of foveal hypoplasia in congenital aniridia with visual acuity, iris phenotype, and PAX6 mutations.
Design: Retrospective case series.
Methods: Ninety-five consecutive patients with high-quality spectral-domain optical coherence tomography records and available genotype were included in a single referral center.
Article Synopsis
- * Researchers analyzed ultrasound data from 22 fetuses with the 6qter deletion, finding significant brain abnormalities such as cerebellar hypoplasia and ventricular enlargement, alongside other structural issues.
- * The results reveal common prenatal sonographic markers for the 6q deletion syndrome and underscore the need for chromosomal microarray analysis to detect related genetic deletions in cases with observed malformations.
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- Inverted duplication deletion 8p (invdupdel(8p)) is a rare genetic condition linked to developmental delays and intellectual disabilities, often presenting with brain abnormalities.
- A study analyzed 36 new cases, revealing that 97% of patients experienced developmental issues, with a significant number also suffering from seizures.
- By comparing this data with 99 previously reported cases, researchers identified a specific 5.1 Mb region in chromosome 8 associated with abnormalities of the corpus callosum, offering insights into potential genetic factors involved.
Single genetic mutations predispose to very early onset inflammatory bowel disease (VEO-IBD). Here, we identify a de novo duplication of the 10p15.1 chromosomal region, including the IL2RA locus, in a 2-year-old girl with treatment-resistant pancolitis that was brought into remission by colectomy.
View Article and Find Full Text PDFCopy Number Variants (CNVs) are an important cause of rare diseases. Array-based Comparative Genomic Hybridization tests yield a ∼12% diagnostic rate, with ∼8% of patients presenting CNVs of unknown significance. CNVs interpretation is particularly challenging on genomic regions outside of those overlapping with previously reported structural variants or disease-associated genes.
View Article and Find Full Text PDFObjective: We aimed to describe epilepsy and EEG patterns related to vigilance states and age, in chromosome15-long-arm-duplication-syndrome (dup15q) children with epilepsy, in both duplication types: interstitial (intdup15) and isodicentric (idic15).
Methods: Clinical data and 70 EEGs of 12 patients (5 intdup15, 7 idic15), followed from 4.5 m.
We report two fetal cases carrying a de novo MID1 mutation and presenting with severe hydrothorax, suggesting the expansion of the phenotype of Opitz GBBB syndrome.
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- Structural variants (SVs), like copy number variants (CNVs) and balanced chromosome rearrangements (ABCRs), are often difficult to detect using traditional short-read sequencing methods due to repetitive sequences, which makes long-read technologies like 10X Genomics' Chromium an interesting alternative.* -
- In a study involving 13 patients, short-read sequencing successfully identified known SVs in 10 of them, while the linked-read technology also detected 10 SVs, including one additional variant missed by the short-read method.* -
- Ultimately, the study concluded that the 10X Genomics linked-read strategy did not significantly enhance the detection or characterization of SVs compared to the short-read sequencing approach.*
Despite advances in neurogenetics of autism spectrum disorders (ASD), many patients fail to be systematically investigated, owing to preconceived ideas, limited access to genetics facilities and inadequacy of consultations to children with behavioural problems. To improve access to services, we reversed the paradigm and delivered on-site genetics consultations to ASD children of Greater Paris day care hospitals and specialized institutions. Since 1998, an ambulatory medical genetics team has been in operation, offering on-site consultations and services to patients and relatives in their usual environment.
View Article and Find Full Text PDFBackground: Neurogenetics investigations and diagnostic yield in patients with autism spectrum disorder (ASD) have significantly improved over the last few years. Yet, many patients still fail to be systematically investigated.
Methods: To improve access to services, an ambulatory team has been established since 1998, delivering on-site clinical genetics consultations and gradually upgrading services to 502 children and young adults with ASD in their standard environment across 26 day-care hospitals and specialized institutions within the Greater Paris region.
Objective: Neural tube defects (NTDs) are one of the most common congenital anomalies caused by a complex interaction of many genetic and environmental factors. In about 10% of cases, NTDs are associated with genetic syndromes or chromosomal anomalies. Among these, SOX3 duplication has been reported in some isolated cases.
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- The study focused on 1p36 deletion syndrome, a genetic condition identified through prenatal testing, noted for developmental delays and facial features.
- Ten new cases were diagnosed around 19 weeks gestation, with deletion sizes varying from 1.6 to 16 Mb, most cases showing no other chromosomal abnormalities.
- Researchers suggest that certain ultrasound findings, like brain and heart defects, should alert doctors to the possibility of this syndrome.