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

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Oliveira, J (Author) Other; Martins, M (Author) Other; Leite, RP (Author) Other; Sousa, M (Author) Other; Santos, R (Author) Other

Journal

Title: Clinical Genetics

Vol. 92

Pages: 434-439

ISSN: 0009-9163

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 14 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6