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Expanding the allelic spectrum of ELOVL4‐related autosomal recessive neuro‐ichthyosis
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Molec Gen Gen Med - 2023 - Alabdulrazzaq - Expanding the allelic spectrum of ELOVL4‐related autosomal recessive.pdf | Published version | 2.23 MB | Adobe PDF | View/Open |
Title: | Expanding the allelic spectrum of ELOVL4‐related autosomal recessive neuro‐ichthyosis |
Authors: | Alabdulrazzaq, F Alanzi, T Al‐Balool, HH Gardham, A Wakeling, E Leitch, HG AlSayed, M Abdulrahim, M Aladwani, A Romito, A Kampe, K Ferdinandusse, S Aboelanine, AH Abdullah, A Alwadani, A Bastaki, L Vaz, FM Bertoli‐Avella, AM Marafi, D |
Item Type: | Journal Article |
Abstract: | Background Very long-chain fatty acids (VLCFAs) composed of more than 20 carbon atoms are essential in the biosynthesis of cell membranes in the brain, skin, and retina. VLCFAs are elongated beyond 28 carbon atoms by ELOVL4 enzyme. Variants in ELOVL4 are associated with three Mendelian disorders: autosomal dominant (AD) Stargardt-like macular dystrophy type 3, AD spinocerebellar ataxia, and autosomal recessive disorder congenital ichthyosis, spastic quadriplegia and impaired intellectual development (ISQMR). Only seven subjects from five unrelated families with ISQMR have been described, all of which have biallelic single-nucleotide variants. Methods We performed clinical exome sequencing on probands from four unrelated families with neuro-ichthyosis. Results We identified three novel homozygous ELOVL4 variants. Two of the families originated from the same Saudi tribe and had the exact homozygous exonic deletion in ELOVL4, while the third and fourth probands had two different novel homozygous missense variants. Seven out of the eight affected subjects had profound developmental delay, epilepsy, axial hypotonia, peripheral hypertonia, and ichthyosis. Delayed myelination and corpus callosum hypoplasia were seen in two of five subjects with brain magnetic rosonance imaging and cerebral atrophy in three. Conclusion Our study expands the allelic spectrum of ELOVL4-related ISQMR. The detection of the same exonic deletion in two unrelated Saudi family from same tribe suggests a tribal founder mutation. |
Issue Date: | Dec-2023 |
Date of Acceptance: | 14-Jul-2023 |
URI: | http://hdl.handle.net/10044/1/106315 |
DOI: | 10.1002/mgg3.2256 |
ISSN: | 2324-9269 |
Publisher: | Wiley |
Start Page: | 1 |
End Page: | 15 |
Journal / Book Title: | Molecular Genetics and Genomic Medicine |
Volume: | 11 |
Issue: | 12 |
Copyright Statement: | © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
Publication Status: | Published |
Article Number: | e2256 |
Online Publication Date: | 2023-08-18 |
Appears in Collections: | Central Faculty |
This item is licensed under a Creative Commons License