Abstract
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.
| Original language | English |
|---|---|
| Journal | Molecular Genetics and Genomic Medicine |
| DOIs | |
| Publication status | Accepted/In press - 2018 Jan 1 |
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Keywords
- congenital scoliosis
- LFNG
- spondylocostal dysostosis
- whole-exome sequencing
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)
Cite this
Screening of known disease genes in congenital scoliosis. / Japan Early Onset Scoliosis Research Group.
In: Molecular Genetics and Genomic Medicine, 01.01.2018.Research output: Contribution to journal › Article
}
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, Koota
AU - Ikegawa, Shiro
PY - 2018/1/1
Y1 - 2018/1/1
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 - congenital scoliosis
KW - LFNG
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
JO - Molecular genetics & genomic medicine
JF - Molecular genetics & genomic medicine
SN - 2324-9269
ER -