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ID 63883
フルテキストURL
著者
Matsuo, Toshihiko Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University ORCID Kaken ID publons researchmap
Chaomulige Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Miyaji, Mary Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hosoya, Osamu Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Saito, Akira StaGen Co., Ltd.
Nakazono, Kazuyuki StaGen Co., Ltd.
抄録
Idiopathic superior oblique muscle palsy is a major type of paralytic, non-comitant strabismus and presents vertical and cyclo-torsional deviation of one eye against the other eye, with a large vertical fusion range and abnormal head posture such as head tilt. Genetic background is considered to play a role in its development, as patients with idiopathic superior oblique muscle palsy have varying degrees of muscle hypoplasia and, rarely, the complete absence of the muscle, that is, aplasia. In this study, whole genome sequencing was performed, and single nucleotide variations and short insertions/deletions (SNVs/InDels) were annotated in two patients each in three small families (six patients in total) with idiopathic superior oblique muscle palsy, in addition to three normal individuals in one family. At first, linkage analysis was carried out in the three families and SNVs/InDels in chromosomal loci with negative LOD scores were excluded. Next, SNVs/InDels shared by the six patients, but not by the three normal individuals, were chosen. SNVs/InDels were further narrowed down by choosing low-frequency (<1%) or non-registered SNVs/InDels in four databases for the Japanese population, and then by choosing SNVs/InDels with functional influence, leading to one candidate gene, SSTR5-AS1 in chromosome 16. The six patients were heterozygous for 13-nucleotide deletion in SSTR5-AS1, except for one homozygous patient, while the three normal individuals were wild type. Targeted polymerase chain reaction (PCR) and direct sequencing of PCR products confirmed the 13-nucleotide deletion in SSTR5-AS1. In the face of newly-registered SSTR5-AS1 13-nucleotide deletion at a higher frequency in a latest released database for the Japanese population, the skipping of low-frequency and non-registration sorting still resulted in only 13 candidate genes including SSTR5-AS1 as common variants. The skipping of linkage analysis also led to the same set of 13 candidate genes. Different testing strategies that consisted of linkage analysis and simple unintentional bioinformatics could reach candidate genes in three small families with idiopathic superior oblique muscle palsy.
キーワード
whole genome sequencing
idiopathic superior oblique muscle palsy
strabismus
esotropia
exotropia
linkage analysis
single nucleotide variations and short insertions/deletions
SNVs/InDels
SSTR5-AS1
bioinformatics
muscle hypoplasia (aplasia)
発行日
2022-08-03
出版物タイトル
International Journal of Molecular Sciences
23巻
15号
出版者
MDPI AG
開始ページ
8626
ISSN
1422-0067
資料タイプ
学術雑誌論文
言語
英語
OAI-PMH Set
岡山大学
著作権者
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.3390/ijms23158626
ライセンス
https://creativecommons.org/licenses/by/4.0/
Citation
Matsuo, T.; Chaomulige; Miyaji, M.; Hosoya, O.; Saito, A.; Nakazono, K. Candidate Genes in Testing Strategies for Linkage Analysis and Bioinformatic Sorting of Whole Genome Sequencing Data in Three Small Japanese Families with Idiopathic Superior Oblique Muscle Palsy. Int. J. Mol. Sci. 2022, 23, 8626. https://doi.org/10.3390/ijms23158626