The complete loss of function of the SMS gene results in a severe form of Snyder-Robinson syndrome.
Genotype-phenotype correlation
Loss of function
Multiple congenital anomalies syndrome
SMS
Snyder-Robinson syndrome
Journal
European journal of medical genetics
ISSN: 1878-0849
Titre abrégé: Eur J Med Genet
Pays: Netherlands
ID NLM: 101247089
Informations de publication
Date de publication:
Apr 2020
Apr 2020
Historique:
received:
04
07
2019
revised:
12
09
2019
accepted:
29
09
2019
pubmed:
4
10
2019
medline:
2
12
2020
entrez:
4
10
2019
Statut:
ppublish
Résumé
Snyder-Robinson syndrome (SRS) is an X-linked syndromic intellectual disability condition caused by variants in the spermine synthase gene (SMS). The syndrome is characterized by facial dysmorphism, thin body build, kyphoscoliosis, osteoporosis, hypotonia, developmental delay and associated neurological features (seizures, unsteady gait, abnormal speech). Until now, only missense variants with a functionally characterized partial loss of function (LoF) have been described. Here we describe the first complete LoF variant, Met303Lysfs*, in a male patient with a severe form of Snyder-Robinson syndrome. He presented with multiple malformations and severly delayed development, and died at 4 months of age. Functional in vitro assays showed a complete absence of functional SMS protein. Taken together, our findings and those of previously reported patients confirm that pathogenic variants of SMS are indeed LoF and that there might exist a genotype-phenotype correlation between the type of variant and the severity of the syndrome.
Identifiants
pubmed: 31580924
pii: S1769-7212(19)30460-4
doi: 10.1016/j.ejmg.2019.103777
pii:
doi:
Substances chimiques
Spermine Synthase
EC 2.5.1.22
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
103777Informations de copyright
Copyright © 2019 Elsevier Masson SAS. All rights reserved.