Novel heterozygous VPS13A pathogenic variants in chorea-neuroacanthocytosis: a case report.

BMC Neurol

Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, No. 106 Zhongshan Er Road, Guangzhou, 510080, China.

Published: October 2023

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary autosomal recessive neurodegenerative disorder caused by pathogenic variants of the Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The variant spectrum of VPS13A has not been completely elucidated. This study reports two novel heterozygous VPS13A pathogenic variants in ChAc that expand the variant spectrum of VPS13A.

Case Presentation: We described a case of a 29-year-old man with typical clinical manifestations of ChAc, including chorea, orofacial lingual dyskinesia, vocal tics, elevated serum biochemical indicators, increased acanthocytes in peripheral blood, and caudate nucleus atrophy. Next-generation sequencing revealed two heterozygous variants of VPS13A: a nonsense variant (NM_033305.2: c.8215G > T, p. Glu2739Ter) and a deletion variant in the exons 25-31.

Conclusion: The identified nonsense variant gives rise to premature translation termination, while the deletion variant is expected to cause a significant in-frame deletion of amino acid residues in the encoded protein. Both variants are considered to be pathogenic and result in loss-of-function proteins. These findings have implications for the genetic counseling of patients with VPS13A variants.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548615PMC
http://dx.doi.org/10.1186/s12883-023-03398-xDOI Listing

Publication Analysis

Top Keywords

pathogenic variants
12
novel heterozygous
8
heterozygous vps13a
8
vps13a pathogenic
8
variant spectrum
8
nonsense variant
8
deletion variant
8
vps13a
6
variants
6
variant
6

Similar Publications

Objective: This prospective clinical study examined the effects of fixed orthodontic appliances on oral hygiene and assessed changes in the oral microflora structure of orthodontic patients using high-throughput sequencing technology.

Methods: A total of 45 patients undergoing initial fixed orthodontic treatment were recruited from three hospitals in Beijing, China. Clinical parameters and oral hygiene habits questionnaire were recorded at pre-treatment (T0) and at a 6-month follow-up (T1).

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the mechanisms of resistance to ceftazidime-avibactam (CZA) in a hypervirulent strain of Klebsiella pneumoniae known as CRE146, which carries the bla gene.
  • Researchers isolated twelve carbapenem-resistant Klebsiella pneumoniae strains from a single patient, employing whole genome sequencing and various pathogenicity tests to understand the virulence factors and resistance development.
  • Findings revealed that the resistance was linked to drug exposure and involved specific genetic mutations in carbapenemase (KPC-228), with CRE146 showing high resistance to CZA while being more susceptible to other antibiotics like meropenem and imipenem.
View Article and Find Full Text PDF

NONO-related X-linked intellectual disability syndrome: further clinical and molecular delineation.

Eur J Med Genet

December 2024

CHU Lille, Institut de Génétique Médicale, F-59000 Lille, France; Univ. Lille, ULR7364 - RADEME - Maladies RAres du DEveloppement embryonnaire et du Métabolisme, F-59000 Lille, France. Electronic address:

The X-linked NONO gene encodes Non-Pou Domain-Containing Octamer-Binding Protein, a multifunctional member of the DBHS family involved in transcriptional regulation, RNA splicing and DNA repair. Pathogenic variants in NONO cause Intellectual Developmental Disorder, X-linked Syndromic (MIM #300967), characterised by intellectual disability, neurodevelopmental delay, cardiomyopathy, such as left ventricular non-compaction (LVNC), and congenital heart defects such as including atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), and patent foramen ovale (PFO). This study reports three new patients with pathogenic hemizygous frameshift variants in NONO identified with exome sequencing, broadening the clinical presentation.

View Article and Find Full Text PDF

O'Donnell-Luria-Rodan (ODLURO) syndrome is an autosomal dominant neurodevelopmental disorder mainly characterized by global development delay/intellectual disability, white matter abnormalities, and behavioral manifestations. It is caused by pathogenic variants in the KMT2E gene. Here we report seven new patients with loss-of-function KMT2E variants, six harboring frameshift/nonsense changes, and one with a 7q22.

View Article and Find Full Text PDF

Catalogue of inherited autosomal recessive disorders found amongst the Roma population of Europe.

Eur J Med Genet

December 2024

Department of Clinical Genetics, Our Lady's Children's Hospital, Children's' Health Ireland, Dublin, Republic of Ireland; Academic Centre on Rare Diseases, University College Dublin, Dublin, Republic of Ireland; National Centre for Inherited Metabolic Disorders, Children's Health Ireland, Temple Street Dublin, Republic of Ireland. Electronic address:

Background: The Roma population are an endogamous, genetically isolated, minority population who migrated from North-Western India to Europe from the 10 Century throughout the Byzantine period and continues to the present day. Approximately 10-12 million Romani people reside in segregated settlements in Europe, and smaller populations live in North America and China. In addition to the endogamy, they also practice consanguinity.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!