X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1.

Détails

ID Serval
serval:BIB_8DE9A339FE79
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
X-linked hypomyelination with spondylometaphyseal dysplasia (H-SMD) associated with mutations in AIFM1.
Périodique
Neurogenetics
Auteur(s)
Miyake N., Wolf N.I., Cayami F.K., Crawford J., Bley A., Bulas D., Conant A., Bent S.J., Gripp K.W., Hahn A., Humphray S., Kimura-Ohba S., Kingsbury Z., Lajoie B.R., Lal D., Micha D., Pizzino A., Sinke R.J., Sival D., Stolte-Dijkstra I., Superti-Furga A., Ulrick N., Taft R.J., Ogata T., Ozono K., Matsumoto N., Neubauer B.A., Simons C., Vanderver A.
ISSN
1364-6753 (Electronic)
ISSN-L
1364-6745
Statut éditorial
Publié
Date de publication
12/2017
Peer-reviewed
Oui
Volume
18
Numéro
4
Pages
185-194
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
An X-linked condition characterized by the combination of hypomyelinating leukodystrophy and spondylometaphyseal dysplasia (H-SMD) has been observed in only four families, with linkage to Xq25-27, and recent genetic characterization in two families with a common AIFM1 mutation. In our study, 12 patients (6 families) with H-SMD were identified and underwent comprehensive assessment accompanied by whole-exome sequencing (WES). Pedigree analysis in all families was consistent with X-linked recessive inheritance. Presentation typically occurred between 12 and 36 months. In addition to the two disease-defining features of spondylometaphyseal dysplasia and hypomyelination on MRI, common clinical signs and symptoms included motor deterioration, spasticity, tremor, ataxia, dysarthria, cognitive defects, pulmonary hypertension, nystagmus, and vision loss due to retinopathy. The course of the disease was slowly progressive. All patients had maternally inherited or de novo mutations in or near exon 7 of AIFM1, within a region of 70 bp, including synonymous and intronic changes. AIFM1 mutations have previously been associated with neurologic presentations as varied as intellectual disability, hearing loss, neuropathy, and striatal necrosis, while AIFM1 mutations in this small region present with a distinct phenotype implicating bone. Analysis of cell lines derived from four patients identified significant reductions in AIFM1 mRNA and protein levels in osteoblasts. We hypothesize that AIFM1 functions in bone metabolism and myelination and is responsible for the unique phenotype in this condition.

Mots-clé
AIFM1 gene, Hypomyelination, Mitochondrial leukodystrophy, Myelin, Spondylometaphyseal dysplasia, Whole exome sequencing (WES)
Pubmed
Open Access
Oui
Création de la notice
12/09/2017 14:32
Dernière modification de la notice
08/05/2019 21:50
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