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

Autor: Becker A; CHRU de Nancy, Laboratoire de Génétique, Inserm U1256, Université de Lorraine, Nancy, France., Felici C; CHRU de Nancy, Laboratoire de Génétique, Inserm U1256, Université de Lorraine, Nancy, France., Lambert L; CHRU de Nancy, Pôle Enfants, Service de Génétique Clinique, Nancy, France.; Inserm U1256, Université de Lorraine, Nancy, France., de Saint Martin A; Hôpital Hautepierre, Centre de référence des épilepsies rares, Strasbourg, France., Abi-Warde MT; Hôpital Hautepierre, Centre de référence des épilepsies rares, Strasbourg, France., Schaefer E; HôpService de Génétique médicale, institut de Génétique médicale d'Alsace, CHU Strasbourg, Strasbourg, France., Zix C; Hôpital de Forbach, Pédiatrie, France., Zamani M; Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.; Narges Medical Genetics and Prenatal Diagnosis Laboratory, Ahvaz, Iran., Sadeghian S; Department of Pediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Zeighami J; Narges Medical Genetics and Prenatal Diagnosis Laboratory, Ahvaz, Iran., Seifi T; Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.; Narges Medical Genetics and Prenatal Diagnosis Laboratory, Ahvaz, Iran., Azizimalamiri R; Department of Pediatric Neurology, Golestan Medical, Educational, and Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Shariati G; Narges Medical Genetics and Prenatal Diagnosis Laboratory, Ahvaz, Iran.; Department of Medical Genetics, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran., Galehdari H; Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran., Selig M; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany., Ding C; Institute of Human Genetics, University Medical Center of the Johannes Gutenberg University, Mainz, Germany., Duerinckx S; IRIBHM, Université Libre de Bruxelles, Brussels, Belgium., Pirson I; IRIBHM, Université Libre de Bruxelles, Brussels, Belgium., Abramowicz M; IRIBHM, Université Libre de Bruxelles, Brussels, Belgium.; Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Clément G; Inserm U1256, Université de Lorraine, Nancy, France.; CHRU de Nancy, Service de neurologie, Nancy, France., Leheup B; CHRU de Nancy, Pôle Enfants, Service de Génétique Clinique, Nancy, France.; Inserm U1256, Université de Lorraine, Nancy, France., Jonveaux P; CHRU de Nancy, Laboratoire de Génétique, Inserm U1256, Université de Lorraine, Nancy, France., Lefort G; CHRU de Nancy, Laboratoire de Génétique, Inserm U1256, Université de Lorraine, Nancy, France., Bronner M; CHRU de Nancy, Laboratoire de Génétique, Inserm U1256, Université de Lorraine, Nancy, France., Renaud M; CHRU de Nancy, Pôle Enfants, Service de Génétique Clinique, Nancy, France.; Inserm U1256, Université de Lorraine, Nancy, France., Bonnet C; CHRU de Nancy, Laboratoire de Génétique, Inserm U1256, Université de Lorraine, Nancy, France.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2023 Mar; Vol. 103 (3), pp. 346-351. Date of Electronic Publication: 2022 Dec 02.
DOI: 10.1111/cge.14264
Abstrakt: 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.
(© 2022 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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