Open AccessScreening of known disease genes in congenital scoliosis
Author(s) -
Takeda Kazuki,
Kou Ikuyo,
Mizumoto Shuji,
Yamada Shuhei,
Kawakami Noriaki,
Nakajima Masahiro,
Otomo Nao,
Ogura Yoji,
Miyake Noriko,
Matsumoto Naomichi,
Kotani Toshiaki,
Sudo Hideki,
Yonezawa Ikuho,
Uno Koki,
Taneichi Hiroshi,
Watanabe Kei,
Shigematsu Hideki,
Sugawara Ryo,
Taniguchi Yuki,
Minami Shohei,
Nakamura Masaya,
Matsumoto Morio,
Watanabe Kota,
Ikegawa Shiro
Publication year - 2018
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.466
Subject(s) - exome sequencing , missense mutation , genetics , compound heterozygosity , medicine , mutation , phenotype , congenital scoliosis , scoliosis , gene duplication , gene , biology
Background Congenital scoliosis (CS) is defined as a lateral curvature of the spine due to the vertebral malformations and has an incidence of 0.5–1/1,000 births. We previously examined TBX6 in Japanese CS patients and revealed that approximately 10% of CS was caused by TBX6 mutations. However, the genetic cause of remaining CS is unknown. Methods We recruited 78 CS patients without TBX6 mutations and major comorbidities, and investigated the genes previously reported to be associated with CS and congenital vertebral malformations by whole‐exome sequencing. Results We identified the compound heterozygous missense variants in LFNG in one patient. No likely disease‐causing variants were identified in other patients, however. LFNG encodes a GlcNAc‐transferase. The LFNG variants showed loss of their enzyme function. Conclusions A LFNG mutation is reported in a case of spondylocostal dysostosis (SCD), a skeletal dysplasia with severe malformations of vertebra and rib. The CS patient with LFNG mutations had multiple vertebral malformations including hemivertebrae, butterfly vertebrae, and block vertebrae, and rib malformations. LFNG mutations may cause a spectrum of phenotypes including CS and SCD. The current list of known disease genes could explain only a small fraction of genetic cause of CS.