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Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review
BACKGROUND: KBG syndrome (OMIM #148050) is a rare, autosomal dominant inherited genetic disorder caused by heterozygous mutations in the ankyrin repeat domain-containing protein 11 (ANKRD11) gene or by microdeletion of chromosome 16q24.3. It is characterized by macrodontia of the upper central incis...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687677/ https://www.ncbi.nlm.nih.gov/pubmed/33262785 http://dx.doi.org/10.3389/fgene.2020.579805 |
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author | Kim, Su Jin Yang, Aram Park, Ji Sun Kwon, Dae Gyu Lee, Jeong-Seop Kwon, Young Se Lee, Ji Eun |
author_facet | Kim, Su Jin Yang, Aram Park, Ji Sun Kwon, Dae Gyu Lee, Jeong-Seop Kwon, Young Se Lee, Ji Eun |
author_sort | Kim, Su Jin |
collection | PubMed |
description | BACKGROUND: KBG syndrome (OMIM #148050) is a rare, autosomal dominant inherited genetic disorder caused by heterozygous mutations in the ankyrin repeat domain-containing protein 11 (ANKRD11) gene or by microdeletion of chromosome 16q24.3. It is characterized by macrodontia of the upper central incisors, distinctive facial dysmorphism, short stature, vertebral abnormalities, hand anomaly including clinodactyly, and various degrees of developmental delay. KBG syndrome presents with variable clinical feature and severity among individuals. Here, we report two KBG patients who have different novel heterozygous mutations of ANKRD11 gene with wide range of clinical manifestations. CASE PRESENTATION: Two novel heterozygous mutations of ANKRD11 gene were identified in two unrelated Korean patients with variable clinical presentations. The first patient presented with short stature and early puberty and was treated with growth hormone and gonadotropin-releasing hormone agonist without adverse effects. He had mild intellectual disability. In targeted exome sequencing, a novel de novo frameshift variant was identified in ANKRD11, c.5889del, and p. (Ile1963MetfsX9). The second patient had severe intellectual disability with epilepsy. He had normal height and prepubertal stage at the age of 11 years. He had behavioral problems such as autism-like features, anxiety, and stereotypical movements. Whole exome sequencing (WES) was performed, and the novel heterozygous mutation, c3310dup, p. (Glu110GlyfsTer5) in ANKRD11 was identified. CONCLUSION: KBG syndrome is often underdiagnosed because of its non-specific features and phenotypic variability. Performing a next—generation sequencing panel, including the ANKRD11 gene for cases of developmental delay with/without short stature may be helpful to identify hitherto undiagnosed KBG syndrome patients. |
format | Online Article Text |
id | pubmed-7687677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-76876772020-11-30 Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review Kim, Su Jin Yang, Aram Park, Ji Sun Kwon, Dae Gyu Lee, Jeong-Seop Kwon, Young Se Lee, Ji Eun Front Genet Genetics BACKGROUND: KBG syndrome (OMIM #148050) is a rare, autosomal dominant inherited genetic disorder caused by heterozygous mutations in the ankyrin repeat domain-containing protein 11 (ANKRD11) gene or by microdeletion of chromosome 16q24.3. It is characterized by macrodontia of the upper central incisors, distinctive facial dysmorphism, short stature, vertebral abnormalities, hand anomaly including clinodactyly, and various degrees of developmental delay. KBG syndrome presents with variable clinical feature and severity among individuals. Here, we report two KBG patients who have different novel heterozygous mutations of ANKRD11 gene with wide range of clinical manifestations. CASE PRESENTATION: Two novel heterozygous mutations of ANKRD11 gene were identified in two unrelated Korean patients with variable clinical presentations. The first patient presented with short stature and early puberty and was treated with growth hormone and gonadotropin-releasing hormone agonist without adverse effects. He had mild intellectual disability. In targeted exome sequencing, a novel de novo frameshift variant was identified in ANKRD11, c.5889del, and p. (Ile1963MetfsX9). The second patient had severe intellectual disability with epilepsy. He had normal height and prepubertal stage at the age of 11 years. He had behavioral problems such as autism-like features, anxiety, and stereotypical movements. Whole exome sequencing (WES) was performed, and the novel heterozygous mutation, c3310dup, p. (Glu110GlyfsTer5) in ANKRD11 was identified. CONCLUSION: KBG syndrome is often underdiagnosed because of its non-specific features and phenotypic variability. Performing a next—generation sequencing panel, including the ANKRD11 gene for cases of developmental delay with/without short stature may be helpful to identify hitherto undiagnosed KBG syndrome patients. Frontiers Media S.A. 2020-11-11 /pmc/articles/PMC7687677/ /pubmed/33262785 http://dx.doi.org/10.3389/fgene.2020.579805 Text en Copyright © 2020 Kim, Yang, Park, Kwon, Lee, Kwon and Lee. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Kim, Su Jin Yang, Aram Park, Ji Sun Kwon, Dae Gyu Lee, Jeong-Seop Kwon, Young Se Lee, Ji Eun Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review |
title | Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review |
title_full | Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review |
title_fullStr | Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review |
title_full_unstemmed | Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review |
title_short | Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review |
title_sort | two novel mutations of ankrd11 gene and wide clinical spectrum in kbg syndrome: case reports and literature review |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687677/ https://www.ncbi.nlm.nih.gov/pubmed/33262785 http://dx.doi.org/10.3389/fgene.2020.579805 |
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