학술논문
Clinically diverse phenotypes and genotypes of patients with branchio-oto-renal syndrome
Document Type
Article
Author
Unzaki, Ai; Morisada, Naoya; Nozu, Kandai; Ye, Ming Juan; Ito, Shuichi; Matsunaga, Tatsuo; Ishikura, Kenji; Ina, Shihomi; Nagatani, Koji; Okamoto, Takayuki; Inaba, Yuji; Ito, Naoko; Igarashi, Toru; Kanda, Shoichiro; Ito, Ken; Omune, Kohei; Iwaki, Takuma; Ueno, Kazuyuki; Yahata, Mayumi; Ohtsuka, Yasufumi; Nishi, Eriko; Takahashi, Nobuya; Ishikawa, Tomoaki; Goto, Shunsuke; Okamoto, Nobuhiko; Iijima, Kazumoto
Source
Journal of Human Genetics; May 2018, Vol. 63 Issue: 5 p647-656, 10p
Subject
Language
ISSN
14345161; 1435232X
Abstract
Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchiogenic anomalies, hearing loss, and renal anomalies. The aim of this study was to reveal the clinical phenotypes and their causative genes in Japanese BOR patients. Patients clinically diagnosed with BOR syndrome were analyzed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array-based comparative genomic hybridization (aCGH), and next-generation sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families; EYA1aberrations were identified in 22 families, SALL1mutations were identified in two families, and SIX1mutations and a 22q partial tetrasomy were identified in one family each. All patients identified with causative genes suffered from hearing loss. Second branchial arch anomalies, including a cervical fistula or cyst, preauricular pits, and renal anomalies, were frequently identified (>60%) in patients with EYA1aberrations. Renal hypodysplasia or unknown-cause renal insufficiency was identified in more than half of patients with EYA1aberrations. Even within the same family, renal phenotypes often varied substantially. In addition to direct sequencing, MLPA and NGS were useful for the genetic analysis of BOR patients.