The new neuromuscular disease related with defects in the ASC-1 complex: report of a second case confirms ASCC1 involvement

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Oliveira, J (Autor) Outra; Martins, M (Autor) Outra; Leite, RP (Autor) Outra; Sousa, M (Autor) Outra; Santos, R (Autor) Outra

Revista

Título: Clinical Genetics

Vol. 92

Páginas: 434-439

ISSN: 0009-9163

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 14 Citações

Outras Informações

ID Authenticus: P-00N-26Y

DOI: 10.1111/cge.12997

Abstract (EN): Next-generation sequencing technology aided the identification of the underlying genetic cause in a female newborn with a severe neuromuscular disorder. The patient presented generalized hypotonia, congenital bone fractures, lack of spontaneous movements and poor respiratory effort. She died within the first days of life. Karyotyping and screening for several genes related with neuromuscular diseases all tested negative. A male sibling was subsequently born with the same clinical presentation. Whole-exome sequencing was performed with variant filtering assuming a recessive disease model. Analysis focused on genes known to be related firstly with congenital myopathies, extended to muscle diseases and finally to other neuromuscular disorders. No disease-causing variants were identified. A similar disorder was described in patients with recessive variants in two genes: TRIP4 (three families) and ASCC1 (one family), both encoding subunits of the nuclear activating signal cointegrator 1 (ASC-1) complex. Our patient was also found to have a homozygous frameshift variant (c.157dupG, p.Glu53Glyfs*19) in ASCC1, thereby representing the second known case. This confirms ASCC1 involvement in a severe neuromuscular disease lying within the spinal muscular atrophy or primary muscle disease spectra.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6