Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: report of three families.

Fiche publication

Date publication

novembre 2022

Journal

Clinical genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Dr BONNET Céline

Tous les auteurs :
Becker A, Felici C, Lambert L, de Saint Martin A, Abi-Warde MT, Schaefer E, Zix C, Zamani M, Sadeghian S, Zeighami J, Seifi T, Azizimalamiri R, Shariati G, Galehdari H, Selig M, Ding C, Duerinckx S, Pirson I, Abramowicz M, Clément G, Leheup B, Jonveaux P, Lefort G, Bronner M, Renaud M, Bonnet C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36371792

Résumé

Bi-allelic variants affecting one of the four genes encoding the AP4 subunits are responsible for the "AP4 deficiency syndrome". Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936). We report on three patients with core features from three unrelated consanguineous families originating from the Middle East. Exome sequencing identified the same homozygous nonsense variant: NM_004722.4(AP4M1):c.1012C>T p.Arg338* (rs146262009). So far, four patients from three other families carrying this homozygous variant have been reported worldwide. We describe their phenotype and compare it to the phenotype of patients with other variants in AP4M1. We construct a shared single-nucleotide polymorphism (SNP) haplotype around AP4M1 in four families and suggest a probable founder effect of Arg338* AP4M1 variant with a common ancestor most likely of Turkish origin. This article is protected by copyright. All rights reserved.