Expanding the allelic spectrum of ELOVL4-related autosomal recessive neuro-ichthyosis.
ELOVL4
autosomal recessive
copy number variant
neuro-ichthyosis
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
27
06
2023
received:
27
02
2023
accepted:
14
07
2023
medline:
18
12
2023
pubmed:
18
8
2023
entrez:
18
8
2023
Statut:
ppublish
Résumé
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. We performed clinical exome sequencing on probands from four unrelated families with neuro-ichthyosis. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
We performed clinical exome sequencing on probands from four unrelated families with neuro-ichthyosis.
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 37592902
doi: 10.1002/mgg3.2256
pmc: PMC10724518
doi:
Substances chimiques
Carbon
7440-44-0
ELOVL4 protein, human
0
Eye Proteins
0
Membrane Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2256Subventions
Organisme : Medical Research Council
ID : MC_UP_1605/2
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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