Publications by authors named "Marion Wandzel"
Background: Spinocerebellar ataxia 27B is the most common genetic late onset cerebellar ataxia (LOCA). However, it commonly overlaps with other genetic LOCA as with the cerebellar form of multiple system atrophy (MSA-C).
Objectives: To pinpoint which clinical signs and symptoms best discriminate between FGF14 + from FGF14 - patients at symptoms' onset.
Article Synopsis
- The study investigates the factors affecting the expansion of tandem repeats, focusing on the FGF14 (GAA)·(TTC) repeat locus in a large sample of 2,530 individuals through advanced sequencing techniques.
- Researchers discovered a prevalent 5'-flanking variant present in over 70% of alleles, which is linked to nonpathogenic alleles and the ancestral lineage of this genetic marker.
- This common variant is associated with greater stability of the tandem repeat during inheritance and improved accessibility of chromatin, suggesting a role in preventing pathological expansion.
Article Synopsis
- Tatton-Brown-Rahman syndrome (TBRS) is a genetic disorder characterized by overgrowth, intellectual disability, and distinct facial features, resulting from mutations in a gene that regulates DNA methylation.* -
- A study of 24 French patients identified 17 new genetic variants, confirming that 100% showed intellectual disability, 96% had distinctive facial traits, and 87% exhibited overgrowth, alongside novel symptoms like hypertrichosis.* -
- The findings enhance the understanding of TBRS's clinical presentation, aiding in diagnosis and patient care by clarifying its genetic and phenotypic diversity.*
The autosomal dominant Okur-Chung neurodevelopmental syndrome (OCNDS: OMIM #617062) is a rare neurodevelopmental disorder first described in 2016. Features include developmental delay (DD), intellectual disability (ID), behavioral problems, hypotonia, language deficits, congenital heart abnormalities, and non-specific dysmorphic facial features. OCNDS is caused by heterozygous pathogenic variants in CSNK2A1 (OMIM *115440; NM_177559.
View Article and Find Full Text PDFBackground: SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability.
Methods: We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor.
Background: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established.
Objectives: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients.
Article Synopsis
- Researchers studied the SCA27B (GAA)•(TTC) repeat locus in over 2,500 individuals to understand factors leading to the expansion of tandem repeats.
- They found a common 17-bp deletion-insertion variation that was present in about 70% of the alleles analyzed.
- This variation was mostly found on alleles with fewer than 30 GAA repeats and contributed to increased stability during meiosis.
Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing.
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- Cutis laxa (CL) is a rare connective tissue disorder with symptoms like wrinkled and sagging skin, and it can sometimes affect other body systems.
- This report focuses on a 17-month-old girl diagnosed with autosomal recessive type 1C cutis laxa (ARCL1C), highlighting a new genetic mutation in the LTBP4 gene that is linked to her condition.
- The study involved genetic testing to explore the effects of a specific nine-base pair deletion in the LTBP4 gene, suggesting its role in causing cutis laxa in this patient.
The risk of adverse effects of nitrous oxide (NO) exposure is insufficiently recognized despite its widespread use. These effects are mainly reported through case reports. We conducted an individual patient data meta-analysis to assess the prevalence of clinical, laboratory, and magnetic resonance findings in association with NO exposure in medical and recreational settings.
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