Screening of known disease genes in congenital scoliosis

Japan Early Onset Scoliosis Research Group

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish
JournalMolecular Genetics and Genomic Medicine
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Scoliosis
Genes
Spine
Mutation
Ribs
Exome
Butterflies
Comorbidity
Parturition
Phenotype
Incidence
Enzymes

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 journalArticle

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title = "Screening of known disease genes in congenital scoliosis",
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.",
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author = "{Japan Early Onset Scoliosis Research Group} and Kazuki Takeda and Ikuyo Kou and Shuji Mizumoto and Shuhei Yamada and Noriaki Kawakami and Masahiro Nakajima and Nao Otomo and Yoji Ogura and Noriko Miyake and Naomichi Matsumoto and Toshiaki Kotani and Hideki Sudo and Ikuho Yonezawa and Koki Uno and Hiroshi Taneichi and Kei Watanabe and Hideki Shigematsu and Ryo Sugawara and Yuki Taniguchi and Shohei Minami and Masaya Nakamura and Morio Matsumoto and Koota Watanabe and Shiro Ikegawa",
year = "2018",
month = "1",
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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

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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

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