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Genetic variant of TTLL11 gene and subsequent ciliary defects are associated with idiopathic scoliosis in a 5-generation UK family

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Hélène Mathieu, Shunmoogum A. Patten, Jose Antonio Aragon-Martin, Louise Ocaka, Michael Simpson, Anne Child, Florina Moldovan

Original languageEnglish
Article number11026
JournalScientific Reports
Issue number1
PublishedDec 2021

Bibliographical note

Funding Information: This study was supported by Yves Cotrel Foundation (to FM, SP, AC) and Scoliosis Research Society (to FM). Marfan Trust UK (to AC and JAAM), Peter and Sonia Field Charitable Trust (to AC) St. George’s University of London (to AC and JAM), This study was also supported by RSBO (Réseau de recherché en Santé Buccodentaire et Osseuse), CHU Sainte-Justine Foundation (to HM) and FRQS (to HM). We thank Mr Michael Garcia BSc for drawing pedigrees and patients for their participation to this project. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Idiopathic scoliosis (IS) is a complex 3D deformation of the spine with a strong genetic component, most commonly found in adolescent girls. Adolescent idiopathic scoliosis (AIS) affects around 3% of the general population. In a 5-generation UK family, linkage analysis identified the locus 9q31.2-q34.2 as a candidate region for AIS; however, the causative gene remained unidentified. Here, using exome sequencing we identified a rare insertion c.1569_1570insTT in the tubulin tyrosine ligase like gene, member 11 (TTLL11) within that locus, as the IS causative gene in this British family. Two other TTLL11 mutations were also identified in two additional AIS cases in the same cohort. Analyses of primary cells of individuals carrying the c.1569_1570insTT (NM_194252) mutation reveal a defect at the primary cilia level, which is less present, smaller and less polyglutamylated compared to control. Further, in a zebrafish, the knock down of ttll11, and the mutated ttll11 confirmed its role in spine development and ciliary function in the fish retina. These findings provide evidence that mutations in TTLL11, a ciliary gene, contribute to the pathogenesis of IS.

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