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Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway

KBG syndrome is a rare genetic disease characterized mainly by skeletal abnormalities, distinctive facial features, and intellectual disability. Heterozygous mutations in ANKRD11 gene, or deletion of 16q24.3 that includes ANKRD11 gene are the cause of KBG syndrome. We describe two patients presentin...

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Autores principales: Zhang, Tingting, Yang, Yun, Yin, Xueling, Wang, Xueqing, Ni, Jihong, Dong, Zhiya, Li, Chuanyin, Lu, Wenli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898801/
https://www.ncbi.nlm.nih.gov/pubmed/33354850
http://dx.doi.org/10.1002/ajmg.a.62024
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author Zhang, Tingting
Yang, Yun
Yin, Xueling
Wang, Xueqing
Ni, Jihong
Dong, Zhiya
Li, Chuanyin
Lu, Wenli
author_facet Zhang, Tingting
Yang, Yun
Yin, Xueling
Wang, Xueqing
Ni, Jihong
Dong, Zhiya
Li, Chuanyin
Lu, Wenli
author_sort Zhang, Tingting
collection PubMed
description KBG syndrome is a rare genetic disease characterized mainly by skeletal abnormalities, distinctive facial features, and intellectual disability. Heterozygous mutations in ANKRD11 gene, or deletion of 16q24.3 that includes ANKRD11 gene are the cause of KBG syndrome. We describe two patients presenting with short stature and partial facial features, whereas no intellectual disability or hearing loss was observed in them. Two ANKRD11 variants, c.4039_4041del (p. Lys1347del) and c.6427C > G (p. Leu2143Val), were identified in this study. Both of them were classified as variants of uncertain significance (VOUS) by ACMG/AMP guidelines and were inherited from their mothers. ANKRD11 could enhance the transactivation of p21 gene, which was identified to participate in chondrogenic differentiation. In this study, we demonstrated that the knockdown of ANKRD11 could reduce the p21‐promoter luciferase activities while re‐introduction of wild type ANKRD11, but not ANKRD11 variants (p. Lys1347del or p. Leu2143Val), could restore the p21 levels. Thus, our study report two loss‐of‐function ANKRD11 variants which might provide new insight on pathogenic mechanism that correlates ANKRD11 variants with the short stature phenotype of KBG syndrome.
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spelling pubmed-78988012021-03-03 Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway Zhang, Tingting Yang, Yun Yin, Xueling Wang, Xueqing Ni, Jihong Dong, Zhiya Li, Chuanyin Lu, Wenli Am J Med Genet A Original Articles KBG syndrome is a rare genetic disease characterized mainly by skeletal abnormalities, distinctive facial features, and intellectual disability. Heterozygous mutations in ANKRD11 gene, or deletion of 16q24.3 that includes ANKRD11 gene are the cause of KBG syndrome. We describe two patients presenting with short stature and partial facial features, whereas no intellectual disability or hearing loss was observed in them. Two ANKRD11 variants, c.4039_4041del (p. Lys1347del) and c.6427C > G (p. Leu2143Val), were identified in this study. Both of them were classified as variants of uncertain significance (VOUS) by ACMG/AMP guidelines and were inherited from their mothers. ANKRD11 could enhance the transactivation of p21 gene, which was identified to participate in chondrogenic differentiation. In this study, we demonstrated that the knockdown of ANKRD11 could reduce the p21‐promoter luciferase activities while re‐introduction of wild type ANKRD11, but not ANKRD11 variants (p. Lys1347del or p. Leu2143Val), could restore the p21 levels. Thus, our study report two loss‐of‐function ANKRD11 variants which might provide new insight on pathogenic mechanism that correlates ANKRD11 variants with the short stature phenotype of KBG syndrome. John Wiley & Sons, Inc. 2020-12-22 2021-03 /pmc/articles/PMC7898801/ /pubmed/33354850 http://dx.doi.org/10.1002/ajmg.a.62024 Text en © 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Zhang, Tingting
Yang, Yun
Yin, Xueling
Wang, Xueqing
Ni, Jihong
Dong, Zhiya
Li, Chuanyin
Lu, Wenli
Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway
title Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway
title_full Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway
title_fullStr Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway
title_full_unstemmed Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway
title_short Two loss‐of‐function ANKRD11 variants in Chinese patients with short stature and a possible molecular pathway
title_sort two loss‐of‐function ankrd11 variants in chinese patients with short stature and a possible molecular pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898801/
https://www.ncbi.nlm.nih.gov/pubmed/33354850
http://dx.doi.org/10.1002/ajmg.a.62024
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