» Articles » PMID: 35955756

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

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2022 Aug 12
PMID 35955756
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Genome-Wide Association Study with Three Control Cohorts of Japanese Patients with Esotropia and Exotropia of Comitant Strabismus and Idiopathic Superior Oblique Muscle Palsy.

Matsuo T, Hamasaki I, Kamatani Y, Kawaguchi T, Yamaguchi I, Matsuda F Int J Mol Sci. 2024; 25(13).

PMID: 39000095 PMC: 11241339. DOI: 10.3390/ijms25136986.


Morphometric Analysis of the Eye by Magnetic Resonance Imaging in Gene-Deficient Mice.

Chaomulige , Matsuo T, Sugimoto K, Miyaji M, Hosoya O, Ueda M Biomedicines. 2024; 12(2).

PMID: 38397974 PMC: 10887158. DOI: 10.3390/biomedicines12020370.

References
1.
Jiang Y, Matsuo T, Fujiwara H, Hasebe S, Ohtsuki H, Yasuda T . ARIX and PHOX2B polymorphisms in patients with congenital superior oblique muscle palsy. Acta Med Okayama. 2005; 59(2):55-62. DOI: 10.18926/AMO/31966. View

2.
Graeber C, Hunter D, Engle E . The genetic basis of incomitant strabismus: consolidation of the current knowledge of the genetic foundations of disease. Semin Ophthalmol. 2013; 28(5-6):427-37. PMC: 4098966. DOI: 10.3109/08820538.2013.825288. View

3.
Cameron D, Schroder J, Sietsma Penington J, Do H, Molania R, Dobrovic A . GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly. Genome Res. 2017; 27(12):2050-2060. PMC: 5741059. DOI: 10.1101/gr.222109.117. View

4.
Taira Y, Matsuo T, Yamane T, Hasebe S, Ohtsuki H . Clinical features of comitant strabismus related to family history of strabismus or abnormalities in pregnancy and delivery. Jpn J Ophthalmol. 2003; 47(2):208-13. DOI: 10.1016/s0021-5155(02)00685-8. View

5.
Xu J, Zou J, Wu L, Lu W . Transcriptome analysis uncovers the diagnostic value of miR-192-5p/HNF1A-AS1/VIL1 panel in cervical adenocarcinoma. Sci Rep. 2020; 10(1):16584. PMC: 7538942. DOI: 10.1038/s41598-020-73523-0. View