Molecular genetic analysis of 30 families with Joubert syndrome
| Autor: | Kenji Ichinomiya, Yoshihiko Shitara, Yasunari Sakai, Aya Inaba, Nobuhiko Okamoto, Kazuyori Yagyu, Naomichi Matsumoto, Kiyoko Sameshima, Adila Al-Kindy, Satoru Takeda, Yumi Habata, Masataka Hisano, Kunimasa Yan, Noriko Miyake, Toshifumi Suzuki, Masato Hiyane, Yasuko Kobayashi, Shuichi Ito, Hideaki Shiraishi, Mai Sato, Kazuhiro Haginoya, Seiji Mizuno, Noboru Fueki, Konomi Shimoda, Yuki Ueda, Kazuhiro Muramatsu, Yumiko Komatsu, Shigemi Kimura, Yu Tsuyusaki, Daisuke Ieda, Hiroshi Suzumura, Hirotomo Saitsu, Yoshinori Tsurusaki, Mitsuko Nakashima, Midori Nakajima, Shinji Saitoh, Kenji Kurosawa, Chikage Yoshizawa |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Oman BBS1 TMEM67 Cell Cycle Proteins Biology Retina Joubert syndrome Genetic Heterogeneity 03 medical and health sciences Japan Antigens Neoplasm Cerebellum Genetics medicine Humans Abnormalities Multiple Genetic Predisposition to Disease Eye Abnormalities Allele Alleles Genetics (clinical) Adaptor Proteins Signal Transducing Membrane Proteins Aplasia Kidney Diseases Cystic medicine.disease Hypoplasia Neoplasm Proteins Pedigree Cytoskeletal Proteins 030104 developmental biology RPGRIP1L Mutation Cerebellar vermis Female Microtubule-Associated Proteins |
| Zdroj: | Clinical Genetics. 90:526-535 |
| ISSN: | 1399-0004 0009-9163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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