Clinically diverse phenotypes and genotypes of patients with branchio-oto-renal syndrome

被引：37

作者：

Unzaki, Ai ^{[1
,2
,3
]}

Morisada, Naoya ^{[1
,4
]}

Nozu, Kandai ^{[1
]}

Ye, Ming Juan ^{[1
]}

Ito, Shuichi ^{[5
]}

Matsunaga, Tatsuo ^{[6
]}

Ishikura, Kenji ^{[7
]}

Ina, Shihomi ^{[8
]}

Nagatani, Koji ^{[9
]}

Okamoto, Takayuki ^{[10
]}

Inaba, Yuji ^{[11
]}

Ito, Naoko ^{[12
]}

Igarashi, Toru ^{[13
]}

Kanda, Shoichiro ^{[14
,15
]}

Ito, Ken ^{[16
]}

Omune, Kohei ^{[17
]}

Iwaki, Takuma ^{[18
]}

Ueno, Kazuyuki ^{[8
]}

Yahata, Mayumi ^{[19
]}

Ohtsuka, Yasufumi ^{[20
]}

Nishi, Eriko ^{[21
]}

Takahashi, Nobuya ^{[22
]}

Ishikawa, Tomoaki ^{[23
]}

Goto, Shunsuke ^{[24
,25
]}

Okamoto, Nobuhiko ^{[21
]}

Iijima, Kazumoto ^{[1
]}

机构：

[1] Kobe Univ, Dept Pediat, Grad Sch Med, Kobe, Hyogo, Japan

[2] Shinshu Univ Hosp, Ctr Med Genet, Matsumoto, Nagano, Japan

[3] Problem Solving Oriented Training Program Adv Me, Matsumoto, Nagano, Japan

[4] Hyogo Prefectural Kobe Childrens Hosp, Dept Clin Genet, Kobe, Hyogo, Japan

[5] Yokohama City Univ, Dept Pediat, Yokohama, Kanagawa, Japan

[6] Natl Hosp Org Tokyo Med Ctr, Dept Otorhinolaryngol, Tokyo, Japan

[7] Natl Ctr Child Hlth & Dev, Div Nephrol & Rheumatol, Tokyo, Japan

[8] Toyama Prefectural Cent Hosp, Dept Pediat, Toyama, Japan

[9] Uwajima City Hosp, Dept Pediat, Uwajima, Japan

[10] Hokkaido Univ, Dept Pediat, Grad Sch Med, Sapporo, Hokkaido, Japan

[11] Nagano Childrens Hosp, Div Neurol, Azumino, Japan

[12] Univ Tsukuba, Fac Med, Dept Kidney & Vasc Pathol, Ibaraki, Japan

[13] Nippon Med Coll Hosp, Dept Pediat, Tokyo, Japan

[14] Univ Tokyo, Dept Pediat, Tokyo, Japan

[15] Tokyo Womens Med Univ, Dept Pediat Nephrol, Tokyo, Japan

[16] JIKEI Univ, Sch Med, Dept Pediat, Tokyo, Japan

[17] Japanese Red Cross Wakayama Med Ctr, Dept Nephrol, Wakayama, Japan

[18] Kagawa Univ, Dept Pediat, Takamatsu, Kagawa, Japan

[19] Tokyo Metropolitan Bokutoh Hosp, Dept Nephrol, Tokyo, Japan

[20] Saga Univ, Dept Pediat, Saga, Japan

[21] Osaka Womens & Childrens Hosp, Dept Med Genet, Osaka, Japan

[22] Yamagata Univ, Dept Pediat, Yamagata, Japan

[23] Nara Med Univ, Dept Pediat, Kashihara, Nara, Japan

[24] Kobe Univ, Grad Sch Med, Div Nephrol, Kobe, Hyogo, Japan

[25] Kobe Univ, Grad Sch Med, Kidney Ctr, Kobe, Hyogo, Japan

来源：

JOURNAL OF HUMAN GENETICS | 2018年 / 63卷 / 05期

关键词：

BOR SYNDROME; KIDNEY DEVELOPMENT; MUTATIONS; EYA1; GENES; SALL1; SIX2;

D O I：

10.1038/s10038-018-0429-8

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 nextgeneration sequencing (NGS). We identified the causative genes in 38/51 patients from 26/36 families; EYA1 aberrations were identified in 22 families, SALL1 mutations were identified in two families, and SIX1 mutations 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 EYA1 aberrations. Renal hypodysplasia or unknown-cause renal insufficiency was identified in more than half of patients with EYA1 aberrations. 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.

引用

页码：647 / 656

页数：10

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