UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Sequence Variants in Three Genes Underlying Leukodystrophy in Pakistani Families

Bibi, F; Haider, N; Din, SU; Shah, M; Krishin, J; Qayyum, N; Raja, GK; ... Ullah, A; + view all (2020) Sequence Variants in Three Genes Underlying Leukodystrophy in Pakistani Families. International Journal of Developmental Neuroscience , 80 (5) pp. 380-388. 10.1002/jdn.10036. Green open access

[thumbnail of Houlden_Sequence Variants in Three Genes Underlying Leukodystrophy in Pakistani Families_AAM.pdf]
Preview
Text
Houlden_Sequence Variants in Three Genes Underlying Leukodystrophy in Pakistani Families_AAM.pdf - Accepted version

Download (10MB) | Preview

Abstract

Leukodystrophies (LDs) are a heterogeneous group of rare and progressive genetic diseases that affect brain, spinal cord, and often the peripheral nerves. They are characterized by abnormal development or destruction of the myelin sheath of the brain. This study was aimed to search for the causative variants in three unrelated consanguineous families presented with LD. Detailed clinical investigations were carried out on probands in three unrelated consanguineous families of Pakistani origin. Targeted gene sequencing and Whole Exome Sequencing (WES) were performed for variant identification. Candidate variants were checked for co‐segregation with the phenotype using Sanger sequencing. Public databases including ExAC, gnomAD, dbSNP, and the 1,000 Genome Project were searched to determine frequencies of the alleles. Conservation of the missense variants was ensured by aligning orthologous protein sequences from diverse vertebrate species. Targeted gene sequencing identified a novel homozygous missense mutation [c.2135G > A, p.(Arg712His) in the ATP Binding Cassette Subfamily D Member 1 (ABCD1; OMIM# 300371) in three affected siblings in family A.WES followed by validation by Sanger sequencing revealed previously reported homozygous missense variants [c.162C > A; p.(Asn54Lys)] in ASPA (OMIM# 608034) in family B and [c.361G > C,p.(Gly121Arg)] in ARSA (OMIM# 607574) in family C. Investigation of three families underlies importance of WES as an amazing diagnostic tool for conclusive determination of a specific type of LD. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families. In addition, searching for common variants in the genes causing LD would help in designing low‐cost targeted variation testing in patients.

Type: Article
Title: Sequence Variants in Three Genes Underlying Leukodystrophy in Pakistani Families
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jdn.10036
Publisher version: https://doi.org/10.1002/jdn.10036
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10099371
Downloads since deposit
24Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item