KIAA1217: A novel candidate gene associated with isolated and syndromic vertebral malformations

被引：16

作者：

Al Dhaheri, Noura ^{[1
,2
]}

Wu, Nan ^{[3
,4
]}

Zhao, Sen ^{[3
]}

Wu, Zhihong ^{[3
]}

Blank, Robert D. ^{[5
]}

Zhang, Jianguo ^{[3
]}

Raggio, Cathy ^{[6
]}

Halanski, Matthew ^{[7
]}

Shen, Jianxiong ^{[3
]}

Noonan, Ken ^{[8
]}

Qiu, Guixing ^{[3
]}

Nemeth, Blaise ^{[8
]}

Sund, Sarah ^{[8
]}

Dunwoodie, Sally L. ^{[9
,10
]}

Chapman, Gavin ^{[9
,10
]}

Glurich, Ingrid ^{[11
]}

Steiner, Robert D. ^{[8
,11
]}

Wohler, Elizabeth ^{[1
]}

Martin, Renan ^{[1
]}

Sobreira, Nara Lygia ^{[1
]}

Giampietro, Philip F. ^{[12
]}

机构：

[1] Johns Hopkins Univ, Sch Med, McKusick Nathans Dept Genet Med, 733 North Broadway St,Suite 569, Baltimore, MD 21205 USA

[2] UAE Univ, Coll Med & Hlth Sci, Dept Pediat, Al Ain, U Arab Emirates

[3] Peking Union Med Coll & Chinese Acad Med Sci, Beijing, Peoples R China

[4] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[5] Med Coll Wisconsin, Milwaukee, WI 53226 USA

[6] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA

[7] Univ Nebraska Med Ctr, Omaha, NE USA

[8] Univ Wisconsin, Madison, WI USA

[9] Victor Chang Cardiac Res Inst, Darlinghurst, NSW, Australia

[10] Univ New South Wales, Sydney, NSW, Australia

[11] Marshfield Clin Fdn Med Res & Educ, Res Inst, Marshfield, WI USA

[12] Rutgers Robert Wood Johnson Med Sch, New Brunswick, NJ USA

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2020年 / 182卷 / 07期

基金：

澳大利亚国家健康与医学研究理事会; 中国国家自然科学基金;

关键词：

cervical vertebral fusion; KIAA1217; spine abnormalities; spine growth and development; vertebral malformation; NOTCH SIGNALING PATHWAY; SEGMENTATION DEFECTS; MUTATION; SCOLIOSIS; VARIANTS;

D O I：

10.1002/ajmg.a.61607

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Vertebral malformations (VMs) are caused by alterations in somitogenesis and may occur in association with other congenital anomalies. The genetic etiology of most VMs remains unknown and their identification may facilitate the development of novel therapeutic and prevention strategies. Exome sequencing was performed on both the discovery cohort of nine unrelated probands from the USA with VMs and the replication cohort from China (Deciphering Disorders Involving Scoliosis & COmorbidities study). The discovery cohort was analyzed using the PhenoDB analysis tool. Heterozygous and homozygous, rare and functional variants were selected and evaluated for their ClinVar, HGMD, OMIM, GWAS, mouse model phenotypes, and other annotations to identify the best candidates. Genes with candidate variants in three or more probands were selected. The replication cohort was analyzed by another in-house developed pipeline. We identified rare heterozygous variants in KIAA1217 in four out of nine probands in the discovery cohort and in five out of 35 probands in the replication cohort. Collectively, we identified 11 KIAA1217 rare variants in 10 probands, three of which have not been described in gnomAD and one of which is a nonsense variant. We propose that genetic variations of KIAA1217 may contribute to the etiology of VMs.

引用

页码：1664 / 1672

页数：9

共 32 条

[31] TBX6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis [J].

Wu, N. ;

Ming, X. ;

Xiao, J. ;

Wu, Z. ;

Chen, X. ;

Shinawi, M. ;

Shen, Y. ;

Yu, G. ;

Liu, J. ;

Xie, H. ;

Gucev, Z. S. ;

Liu, S. ;

Yang, N. ;

Al-Kateb, H. ;

Chen, J. ;

Zhang, Jian ;

Hauser, N. ;

Zhang, T. ;

Tasic, V. ;

Liu, P. ;

Su, X. ;

Pan, X. ;

Liu, C. ;

Wang, L. ;

Shen, Joseph ;

Shen, Jianxiong ;

Chen, Y. ;

Zhang, T. ;

Zhang, Jianguo ;

Choy, K. W. ;

Wang, Jun ;

Wang, Q. ;

Li, S. ;

Zhou, W. ;

Guo, J. ;

Wang, Y. ;

Zhang, C. ;

Zhao, H. ;

An, Y. ;

Zhao, Y. ;

Wang, Jiucun ;

Liu, Z. ;

Zuo, Y. ;

Tian, Y. ;

Weng, X. ;

Sutton, V. R. ;

Wang, H. ;

Ming, Y. ;

Kulkarni, S. ;

Zhong, T. P. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :341-350

[32] Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies [J].

Ye, Ming ;

Berry-Wynne, Karyn M. ;

Asai-Coakwell, Mika ;

Sundaresan, Periasamy ;

Footz, Tim ;

French, Curtis R. ;

Abitbol, Marc ;

Fleisch, Valerie C. ;

Corbett, Nathan ;

Allison, W. Ted ;

Drummond, Garry ;

Walter, Michael A. ;

Underhill, T. Michael ;

Waskiewicz, Andrew J. ;

Lehmann, Ordan J. .

HUMAN MOLECULAR GENETICS, 2010, 19 (02) :287-298

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