TY - JOUR
T1 - Screening of known disease genes in congenital scoliosis
AU - Japan Early Onset Scoliosis Research Group
AU - Takeda, Kazuki
AU - Kou, Ikuyo
AU - Mizumoto, Shuji
AU - Yamada, Shuhei
AU - Kawakami, Noriaki
AU - Nakajima, Masahiro
AU - Otomo, Nao
AU - Ogura, Yoji
AU - Miyake, Noriko
AU - Matsumoto, Naomichi
AU - Kotani, Toshiaki
AU - Sudo, Hideki
AU - Yonezawa, Ikuho
AU - Uno, Koki
AU - Taneichi, Hiroshi
AU - Watanabe, Kei
AU - Shigematsu, Hideki
AU - Sugawara, Ryo
AU - Taniguchi, Yuki
AU - Minami, Shohei
AU - Nakamura, Masaya
AU - Matsumoto, Morio
AU - Watanabe, Kota
AU - Ikegawa, Shiro
N1 - Funding Information:
We are very grateful to the individuals who participated in this study. We thank T. Oguma, T. Kusadokoro, Y. Taka-nashi, and S. Tominaga for technical assistance and Dr. Stephen P. Robertson (Univ. of Otago) and Satoko Hakusui (Meijo Univ.) for experimental advices and technical assistance, respectively. This study was supported by research grants from Japan Agency for Medical Research and Development (AMED) (contract No. 17ek0109280h00011 for S.I., and N.M. and contract No. 17bm0804006h0001 and 17ek0109212h0001 for S.I.), Japan Orthopaedics and Traumatology Foundation (for K.T.) and Grant‐in‐Aid for Scientific Research (C) 16K08251 (for Sh.M.) from the Japan Society for the Promotion of Science, Japan.
Funding Information:
We are very grateful to the individuals who participated in this study. We thank T. Oguma, T. Kusadokoro, Y. Takanashi, and S. Tominaga for technical assistance and Dr. Stephen P. Robertson (Univ. of Otago) and Satoko Hakusui (Meijo Univ.) for experimental advices and technical assistance, respectively. This study was supported by research grants from Japan Agency for Medical Research and Development (AMED) (contract No. 17ek0109280h00011 for S.I., and N.M. and contract No. 17bm0804006h0001 and 17ek0109212h0001 for S.I.), Japan Orthopaedics and Traumatology Foundation (for K.T.) and Grant-in-Aid for Scientific Research (C) 16K08251 (for Sh.M.) from the Japan Society for the Promotion of Science, Japan.
Publisher Copyright:
© 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - LFNG
KW - congenital scoliosis
KW - spondylocostal dysostosis
KW - whole-exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85052964265&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052964265&partnerID=8YFLogxK
U2 - 10.1002/mgg3.466
DO - 10.1002/mgg3.466
M3 - Article
C2 - 30196550
AN - SCOPUS:85052964265
VL - 6
SP - 966
EP - 974
JO - Molecular genetics & genomic medicine
JF - Molecular genetics & genomic medicine
SN - 2324-9269
IS - 6
ER -