Paternal mosaicism of an STXBP1 mutation in OS

Saitsu H, Hoshino H, Kato M, Nishiyama K, Okada I, Yoneda Y, Tsurusaki Y, Doi H, Miyake N, Kubota M, Hayasaka K, Matsumoto N. Paternal mosaicism of an STXBP1 mutation in OS. Ohtahara syndrome (OS) is one of the most severe and earliest forms of epilepsy. We have recently identified that the de novo...

Full description

Saved in:
Bibliographic Details
Published in:Clinical genetics 2011-11, Vol.80 (5), p.484-488
Main Authors: Saitsu, H, Hoshino, H, Kato, M, Nishiyama, K, Okada, I, Yoneda, Y, Tsurusaki, Y, Doi, H, Miyake, N, Kubota, M, Hayasaka, K, Matsumoto, N
Format: Article
Language:English
Subjects:
Age
Biological and medical sciences
Blood
EEG
Epilepsy
Epilepsy - genetics
Exons
Fathers
Female
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetics
Genetics of eukaryotes. Biological and molecular evolution
HRM analysis
Humans
Infant
Infant, Newborn
Insertion
Introns
Male
Medical genetics
Medical sciences
Melting
Molecular and cellular biology
Mosaicism
Mosaics
Munc18 Proteins - genetics
Mutation
Nails
Nonsense mutation
nonsense-mediated mRNA decay
Polymerase chain reaction
Saliva
somatic mosaicism
Spasms, Infantile - genetics
Splicing
STXBP1
Transcription
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Saitsu H, Hoshino H, Kato M, Nishiyama K, Okada I, Yoneda Y, Tsurusaki Y, Doi H, Miyake N, Kubota M, Hayasaka K, Matsumoto N. Paternal mosaicism of an STXBP1 mutation in OS. Ohtahara syndrome (OS) is one of the most severe and earliest forms of epilepsy. We have recently identified that the de novo mutations of STXBP1 are important causes for OS. Here we report a paternal somatic mosaicism of an STXBP1 mutation. The affected daughter had onset of spasms at 1 month of age, and interictal electroencephalogram showed suppression‐burst pattern, leading to the diagnosis of OS. She had a heterozygous c.902+5G>A mutation of STXBP1, which affects donor splicing of exon 10, resulting in 138‐bp insertion of intron 10 sequences in the transcript. The mutant transcript had a premature stop codon, and was degraded by nonsense‐mediated mRNA decay in lymphoblastoid cells derived from the patient. High‐resolution melting analysis of clinically unaffected parental DNAs suggested that the father was somatic mosaic for the mutation, which was also suggested by sequencing. Cloning of PCR products amplified with the paternal DNA samples extracted from blood, saliva, buccal cells, and nails suggested that 5.3%, 8.7%, 11.9%, and 16.9% of alleles harbored the mutation, respectively. This is a first report of somatic mosaicism of an STXBP1 mutation, which has implications in genetic counseling of OS.
ISSN:0009-9163
1399-0004
DOI:10.1111/j.1399-0004.2010.01575.x