Open this publication in new window or tab >>Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74000, Pakistan..
Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74000, Pakistan..
Iqra Natl Univ, Dept Allied Hlth Sci, Swat Campus, Swat 19200, Pakistan..
Univ Med Ctr Gottingen, Inst Human Genet, D-37073 Gottingen, Germany.;Univ Med Ctr Gottingen, Inst Auditory Neurosci, D-37075 Gottingen, Germany.;Univ Med Ctr Gottingen, InnerEarLab, D-37075 Gottingen, Germany..
Pir Mehr Ali Shah Arid Agr Univ Rawalpindi PMAS AA, Univ Inst Biochem & Biotechnol UIBB, Rawalpindi 46300, Pakistan..
Pakistan Inst Engn & Appl Sci PIEAS, Natl Inst Biotechnol & Genet Engn Coll NIBGE C, Hlth Biotechnol Div, Human Mol Genet Lab, Islamabad 44000, Pakistan..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
UCL Queen Sq Inst Neurol, Dept Neuromuscular Disorders, London WC1N 3BG, England..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
UCL Queen Sq Inst Neurol, Dept Neuromuscular Disorders, London WC1N 3BG, England..
Univ Oslo, Inst Clin Med, POB 1171, N-0318 Oslo, Norway.;Oslo Univ Hosp, Dept Neurol, POB 4950 Nydalen, N-0424 Oslo, Norway..
Pakistan Inst Engn & Appl Sci PIEAS, Natl Inst Biotechnol & Genet Engn Coll NIBGE C, Hlth Biotechnol Div, Human Mol Genet Lab, Islamabad 44000, Pakistan.;Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74000, Pakistan..
Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74000, Pakistan..
Oslo Univ Hosp, Dept Neurol, POB 4950 Nydalen, N-0424 Oslo, Norway..
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2023 (English)In: Genes, ISSN 2073-4425, E-ISSN 2073-4425, Vol. 14, no 7, article id 1404Article in journal (Refereed) Published
Abstract [en]
Spinocerebellar disorders are a vast group of rare neurogenetic conditions, generally characterized by overlapping clinical symptoms including progressive cerebellar ataxia, spastic paraparesis, cognitive deficiencies, skeletal/muscular and ocular abnormalities. The objective of the present study is to identify the underlying genetic causes of the rare spinocerebellar disorders in the Pakistani population. Herein, nine consanguineous families presenting different spinocerebellar phenotypes have been investigated using whole exome sequencing. Sanger sequencing was performed for segregation analysis in all the available individuals of each family. The molecular analysis of these families identified six novel pathogenic/likely pathogenic variants; ZFYVE26: c.1093del, SACS: c.1201C>T, BICD2: c.2156A>T, ALS2: c.2171-3T>G, ALS2: c.3145T>A, and B4GALNT1: c.334_335dup, and three already reported pathogenic variants; FA2H: c.159_176del, APTX: c.689T>G, and SETX: c.5308_5311del. The clinical features of all patients in each family are concurrent with the already reported cases. Hence, the current study expands the mutation spectrum of rare spinocerebellar disorders and implies the usefulness of next-generation sequencing in combination with clinical investigation for better diagnosis of these overlapping phenotypes.
Place, publisher, year, edition, pages
MDPI AG, 2023
Keywords
spinocerebellar, consanguinity, ataxia, spastic paraplegia, neurological disorders
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-509147 (URN)10.3390/genes14071404 (DOI)001035939200001 ()37510308 (PubMedID)
Funder
The Swedish Brain Foundation
2023-08-162023-08-162023-08-16Bibliographically approved