Molecular genetics & genomic medicine · 2023
Expanding the allelic spectrum of ELOVL4-related autosomal recessive neuro-ichthyosis.
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Alabdulrazzaq Fatima, Alanzi Talal, Al-Balool Haya H, Gardham Alice, Wakeling Emma, Leitch Harry G, AlSayed Moeenaldeen, Abdulrahim Maha, Aladwani Abdulaziz, Romito Antonio, Kampe Kapil, Ferdinandusse Sacha, Aboelanine Ashraf H, Abdullah Amira, Alwadani Amal, Bastaki Laila, Vaz Frédéric M, Bertoli-Avella Aida M, Marafi Dana
Аннотация
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.
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.