Molecular genetic analysis of 30 families with Joubert syndrome

被引：47

作者：

Suzuki, T. ^{[1
,2
]}

Miyake, N. ^{[1
]}

Tsurusaki, Y. ^{[3
]}

Okamoto, N. ^{[4
]}

Alkindy, A. ^{[5
]}

Inaba, A. ^{[6
]}

Sato, M. ^{[7
]}

Ito, S. ^{[8
]}

Muramatsu, K. ^{[9
]}

Kimura, S. ^{[10
]}

Ieda, D. ^{[11
]}

Saitoh, S. ^{[11
]}

Hiyane, M. ^{[12
]}

Suzumura, H.

Yagyu, K. ^{[13
]}

Shiraishi, H. ^{[14
]}

Nakajima, M. ^{[14
]}

Fueki, N. ^{[15
]}

Habata, Y. ^{[16
]}

Ueda, Y.

Komatsu, Y. ^{[17
]}

Yan, K. ^{[17
]}

Shimoda, K. ^{[18
]}

Shitara, Y. ^{[18
]}

Mizuno, S. ^{[19
]}

Ichinomiya, K. ^{[20
]}

Sameshima, K. ^{[21
]}

Tsuyusaki, Y. ^{[22
]}

Kurosawa, K. ^{[23
]}

Sakai, Y. ^{[24
]}

Haginoya, K. ^{[25
]}

Kobayashi, Y. ^{[9
,26
]}

Yoshizawa, C. ^{[9
]}

Hisano, M. ^{[27
]}

Nakashima, M. ^{[1
]}

Saitsu, H. ^{[1
,28
]}

Takeda, S. ^{[2
]}

Matsumoto, N. ^{[1
]}

机构：

[1] Yokohama City Univ, Dept Human Genet, Grad Sch Med, Yokohama, Kanagawa 2360004, Japan

[2] Juntendo Univ, Dept Obstet & Gynecol, Fac Med, Tokyo, Japan

[3] Kanagawa Childrens Med Ctr, Clin Res Inst, Yokohama, Kanagawa, Japan

[4] Osaka Med Ctr & Res Inst Maternal & Child Hlth, Dept Med Genet, Osaka, Japan

[5] Sultan Qaboos Univ Hosp, Dept Genet, Muscat, Oman

[6] Yokohama City Univ, Childrens Med Ctr, Med Ctr, Yokohama, Kanagawa, Japan

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

[8] Yokohama City Univ, Grad Sch Med, Dept Pediat, Yokohama, Kanagawa, Japan

[9] Gunma Univ, Dept Pediat, Grad Sch Med, Gunma, Japan

[10] Kumamoto City Child Dev Support Ctr, Kumamoto, Japan

[11] Nagoya City Univ, Dept Pediat & Neonatol, Grad Sch Med Sci, Nagoya, Aichi, Japan

[12] Okinawa Prefectural Southern Med Ctr & Childrens, Div Child Neurol, Okinawa, Japan

[13] Hokkaido Univ, Dept Child & Adolescent Psychiat, Grad Sch Med, Sapporo, Hokkaido, Japan

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

[15] Nagano Childrens Hosp, Div Rehabil, Nagano, Japan

[16] Hokkaido Med Ctr Child Hlth & Rehabil, Dept Pediat Rehabil, Sapporo, Hokkaido, Japan

[17] Kyorin Univ, Dept Pediat, Sch Med, Tokyo, Japan

[18] Univ Tokyo, Grad Sch Med, Dept Pediat, Tokyo, Japan

[19] Aichi Human Serv Ctr, Cent Hosp, Dept Pediat, Aichi, Japan

[20] Gunma Childrens Med Ctr, Dept Neonatol, Gunma, Japan

[21] Gunma Childrens Med Ctr, Div Med Genet, Gunma, Japan

[22] Kanagawa Childrens Med Ctr, Div Neurol, Clin Res Inst, Yokohama, Kanagawa, Japan

[23] Kanagawa Childrens Med Ctr, Div Med Genet, Clin Res Inst, Yokohama, Kanagawa, Japan

[24] Kyushu Univ, Grad Sch Med Sci, Dept Pediat, Fukuoka, Japan

[25] Miyagi Childrens Hosp, Dept Pediat Neurol, Sendai, Miyagi, Japan

[26] Univ Bristol, Acad Renal Unit, Sch Clin Sci, Bristol, Avon, England

[27] Chiba Childrens Hosp, Dept Nephrol, Chiba, Japan

[28] Hamamatsu Univ Sch Med, Dept Biochem, Hamamatsu, Shizuoka, Japan

来源：

CLINICAL GENETICS | 2016年 / 90卷 / 06期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

concomitant mutations; Japanese; Joubert syndrome; Whole-exome sequencing; SYNDROME-RELATED DISORDERS; CENTROSOMAL PROTEIN; DIAGNOSTIC UTILITY; FRENCH-CANADIANS; TRANSITION ZONE; MECKEL-SYNDROME; MUTATIONS; RPGRIP1L; CILIOPATHIES; CILIOGENESIS;

D O I：

10.1111/cge.12836

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Joubert syndrome (JS) is rare recessive disorders characterized by the combination of hypoplasia/aplasia of the cerebellar vermis, thickened and elongated superior cerebellar peduncles, and a deep interpeduncular fossa which is defined by neuroimaging and is termed the molar tooth sign'. JS is genetically highly heterogeneous, with at least 29 disease genes being involved. To further understand the genetic causes of JS, we performed whole-exome sequencing in 24 newly recruited JS families. Together with six previously reported families, we identified causative mutations in 25 out of 30 (24+6) families (83.3%). We identified eight mutated genes in 27 (21+6) Japanese families, TMEM67 (7/27, 25.9%) and CEP290 (6/27, 22.2%) were the most commonly mutated. Interestingly, 9 of 12 CEP290 disease alleles were c.6012-12T>A (75.0%), an allele that has not been reported in non-Japanese populations. Therefore c.6012-12T>A is a common allele in the Japanese population. Importantly, one Japanese and one Omani families carried compound biallelic mutations in two distinct genes (TMEM67/RPGRIP1L and TMEM138/BBS1, respectively). BBS1 is the causative gene in Bardet-Biedl syndrome. These concomitant mutations led to severe and/or complex clinical features in the patients, suggesting combined effects of different mutant genes.

引用

页码：526 / 535

页数：10

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