Dataset Information

Genetic investigation of patients with autosomal recessive ataxia and identification of two novel variants in the SQSTM1 and SYNE1 genes.

ABSTRACT: Hereditary ataxias are classified by inheritance patterns into autosomal dominant, autosomal recessive, X-linked, and mitochondrial modes of inheritance. A large group of adult hereditary ataxias have autosomal dominant inheritance, and autosomal recessive cerebellar ataxias (ARCAs) are rare, with greater diversity in phenotypic and genotypic features. Therefore, comprehensive genetic testing is useful for identifying the genes responsible for ARCAs. We identified two novel pathogenic variants of the SQSTM1 and SYNE1 genes via whole-exome sequencing in patients with ARCAs.

SUBMITTER: Mokhtari D

PROVIDER: S-EPMC11364807 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic investigation of patients with autosomal recessive ataxia and identification of two novel variants in the SQSTM1 and SYNE1 genes.

Mokhtari Diana D Jahanpanah Mohammad M Jabbari Nasim N Azari Hamed H Davarnia Sana S Mokaber Haleh H Arish Sara S Molatefi Rasol R Abbasi Vahid V Davarnia Behzad B

Human genome variation 20240830 1

Hereditary ataxias are classified by inheritance patterns into autosomal dominant, autosomal recessive, X-linked, and mitochondrial modes of inheritance. A large group of adult hereditary ataxias have autosomal dominant inheritance, and autosomal recessive cerebellar ataxias (ARCAs) are rare, with greater diversity in phenotypic and genotypic features. Therefore, comprehensive genetic testing is useful for identifying the genes responsible for ARCAs. We identified two novel pathogenic variants o ...[more]

PMID: 39214971

Similar Datasets

Project description:Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene have been reported to cause a relatively pure, slowly progressive cerebellar recessive ataxia mostly identified in Quebec, Canada. Combining next-generation sequencing techniques and deep-phenotyping (clinics, magnetic resonance imaging, positron emission tomography, muscle histology), we here established the frequency, phenotypic spectrum and genetic spectrum of SYNE1 in a screening of 434 non-Canadian index patients from seven centres across Europe. Patients were screened by whole-exome sequencing or targeted panel sequencing, yielding 23 unrelated families with recessive truncating SYNE1 mutations (23/434 = 5.3%). In these families, 35 different mutations were identified, 34 of them not previously linked to human disease. While only 5/26 patients (19%) showed the classical SYNE1 phenotype of mildly progressive pure cerebellar ataxia, 21/26 (81%) exhibited additional complicating features, including motor neuron features in 15/26 (58%). In three patients, respiratory dysfunction was part of an early-onset multisystemic neuromuscular phenotype with mental retardation, leading to premature death at age 36 years in one of them. Positron emission tomography imaging confirmed hypometabolism in extra-cerebellar regions such as the brainstem. Muscle biopsy reliably showed severely reduced or absent SYNE1 staining, indicating its potential use as a non-genetic indicator for underlying SYNE1 mutations. Our findings, which present the largest systematic series of SYNE1 patients and mutations outside Canada, revise the view that SYNE1 ataxia causes mainly a relatively pure cerebellar recessive ataxia and that it is largely limited to Quebec. Instead, complex phenotypes with a wide range of extra-cerebellar neurological and non-neurological dysfunctions are frequent, including in particular motor neuron and brainstem dysfunction. The disease course in this multisystemic neurodegenerative disease can be fatal, including premature death due to respiratory dysfunction. With a relative frequency of ∼5%, SYNE1 is one of the more common recessive ataxias worldwide.

Dataset Information

Genetic investigation of patients with autosomal recessive ataxia and identification of two novel variants in the SQSTM1 and SYNE1 genes.

Publications

Genetic investigation of patients with autosomal recessive ataxia and identification of two novel variants in the SQSTM1 and SYNE1 genes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets