A new case of SMABF2 diagnosed in stillbirth expands the prenatal presentation and mutational spectrum of ASCC1.
Carrier Proteins
/ genetics
Codon, Nonsense
/ genetics
Congenital Abnormalities
/ diagnosis
DNA Copy Number Variations
/ genetics
Exome
/ genetics
Female
Fractures, Bone
/ diagnosis
Genetic Association Studies
Genetic Testing
Humans
Male
Muscular Atrophy, Spinal
/ diagnosis
Mutation, Missense
/ genetics
Pedigree
Pregnancy
Stillbirth
/ epidemiology
Exome Sequencing
ASCC1
SMABF2
arthrogryposis
microdeletion
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
15
07
2019
revised:
30
10
2019
accepted:
02
11
2019
pubmed:
28
12
2019
medline:
5
1
2021
entrez:
28
12
2019
Statut:
ppublish
Résumé
Spinal muscular atrophy with congenital bone fractures 2 (SMABF2) is a rare autosomal recessive neuromuscular disorder characterized by arthrogryposis multiplex congenita and prenatal fractures of the long bones, with poor prognosis. The most affected patients present with biallelic loss-of-function nucleotide variants in ASCC1 gene, coding a subunit of the transcriptional coactivator ASC-1 complex, although the exact pathogenesis is yet unknown. This work describes the first case of SMABF2 in a stillbirth with documented evolution of the disease in the prenatal period. A microdeletion copy number variant (CNV) of about 64 Kb, involving four exons of ASCC1, was firstly detected by microarray analysis, requested for arthrogryposis and hydrops. Subsequent exome analysis disclosed a nucleotide variant of the same gene [c.1027C>T; (p. Arg343*)], resulting in the introduction of a premature termination codon. This stillbirth represents the first case of ASCC1 compound heterozygosity, due to an exonic microdeletion and a nucleotide variant, expanding the mutational spectrum of this gene. It also provides further evidence that exonic CNVs are an underestimated cause of disease-alleles and that the integrated use of the last generation genetic analysis tools, together with careful clinical evaluations, are fundamental for the characterization of rare diseases even in the prenatal setting.
Identifiants
pubmed: 31880396
doi: 10.1002/ajmg.a.61431
doi:
Substances chimiques
ASCC1 protein, human
0
Carrier Proteins
0
Codon, Nonsense
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
508-512Subventions
Organisme : Italian Ministry of Health
ID : Ricerca Corrente 2019
Pays : International
Informations de copyright
© 2019 Wiley Periodicals, Inc.
Références
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