In:
Clinical Genetics, Wiley, Vol. 89, No. 2 ( 2016-02), p. 198-204
Abstract:
Infantile spasms syndrome ( ISs ) is characterized by clinical spasms with ictal electrodecrement, usually occurring before the age of 1 year and frequently associated with cognitive impairment. Etiology is widely heterogeneous, the cause remaining elusive in 40% of patients. We searched for de novo mutations in 10 probands with ISs and their parents using whole‐exome sequencing ( WES ). Patients had neither consanguinity nor family history of epilepsy. Common causes of ISs were excluded by brain magnetic resonance imaging ( MRI ), metabolic screening, array‐comparative genomic hybridization ( CGH ) and testing for mutations in CDKL5 , STXBP1 , and for ARX duplications. We found a probably pathogenic mutation in four patients. Missense mutations in SCN2A (p. Leu1342Pro ) and KCNQ2 (p. Ala306Thr ) were found in two patients with no history of epilepsy before the onset of ISs . The p. Asn107Ser missense mutation of ALG13 had been previously reported in four females with ISs . The fourth mutation was an in‐frame deletion (p.Phe110del) in NR2F1 , a gene whose mutations cause intellectual disability, epilepsy, and optic atrophy. In addition, we found a possibly pathogenic variant in KIF3C that encodes a kinesin expressed during neural development. Our results confirm that WES improves significantly the diagnosis yield in patients with sporadic ISs .
Type of Medium:
Online Resource
ISSN:
0009-9163
,
1399-0004
DOI:
10.1111/cge.2016.89.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2004581-5
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