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A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family
BACKGROUND: Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In th...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206816/ https://www.ncbi.nlm.nih.gov/pubmed/32380970 http://dx.doi.org/10.1186/s12881-020-01038-6 |
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author | Khan, Sher Alam Khan, Muhammad Adnan Muhammad, Nazif Bashir, Hina Khan, Niamat Muhammad, Noor Yilmaz, Rüstem Khan, Saadullah Wasif, Naveed |
author_facet | Khan, Sher Alam Khan, Muhammad Adnan Muhammad, Nazif Bashir, Hina Khan, Niamat Muhammad, Noor Yilmaz, Rüstem Khan, Saadullah Wasif, Naveed |
author_sort | Khan, Sher Alam |
collection | PubMed |
description | BACKGROUND: Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individuals, the enamel is usually thin, soft, rough, brittle, pitted, chipped, and abraded, having reduced functional ability and aesthetics. It leads to severe complications in the patient, like early tooth loss, severe discomfort, pain, dental caries, chewing difficulties, and discoloration of teeth from yellow to yellowish-brown or creamy type. The study aimed to identify the disease-causing variant in a consanguineous family. METHODS: We recruited a consanguineous Pashtun family of Pakistani origin. Exome sequencing analysis was followed by Sanger sequencing to identify the pathogenic variant in this family. RESULTS: Clinical analysis revealed hypomaturation AI having generalized yellow-brown or creamy type of discoloration in affected members. We identified a novel nonsense sequence variant c.1192C > T (p.Gln398*) in exon-12 of SLC24A4 by using exome sequencing. Later, its co-segregation within the family was confirmed by Sanger sequencing. The human gene mutation database (HGMD, 2019) has a record of five pathogenic variants in SLC24A4, causing AI phenotype. CONCLUSION: This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare AI type in humans. |
format | Online Article Text |
id | pubmed-7206816 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72068162020-05-15 A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family Khan, Sher Alam Khan, Muhammad Adnan Muhammad, Nazif Bashir, Hina Khan, Niamat Muhammad, Noor Yilmaz, Rüstem Khan, Saadullah Wasif, Naveed BMC Med Genet Research Article BACKGROUND: Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individuals, the enamel is usually thin, soft, rough, brittle, pitted, chipped, and abraded, having reduced functional ability and aesthetics. It leads to severe complications in the patient, like early tooth loss, severe discomfort, pain, dental caries, chewing difficulties, and discoloration of teeth from yellow to yellowish-brown or creamy type. The study aimed to identify the disease-causing variant in a consanguineous family. METHODS: We recruited a consanguineous Pashtun family of Pakistani origin. Exome sequencing analysis was followed by Sanger sequencing to identify the pathogenic variant in this family. RESULTS: Clinical analysis revealed hypomaturation AI having generalized yellow-brown or creamy type of discoloration in affected members. We identified a novel nonsense sequence variant c.1192C > T (p.Gln398*) in exon-12 of SLC24A4 by using exome sequencing. Later, its co-segregation within the family was confirmed by Sanger sequencing. The human gene mutation database (HGMD, 2019) has a record of five pathogenic variants in SLC24A4, causing AI phenotype. CONCLUSION: This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare AI type in humans. BioMed Central 2020-05-07 /pmc/articles/PMC7206816/ /pubmed/32380970 http://dx.doi.org/10.1186/s12881-020-01038-6 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Khan, Sher Alam Khan, Muhammad Adnan Muhammad, Nazif Bashir, Hina Khan, Niamat Muhammad, Noor Yilmaz, Rüstem Khan, Saadullah Wasif, Naveed A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family |
title | A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family |
title_full | A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family |
title_fullStr | A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family |
title_full_unstemmed | A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family |
title_short | A novel nonsense variant in SLC24A4 causing a rare form of amelogenesis imperfecta in a Pakistani family |
title_sort | novel nonsense variant in slc24a4 causing a rare form of amelogenesis imperfecta in a pakistani family |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206816/ https://www.ncbi.nlm.nih.gov/pubmed/32380970 http://dx.doi.org/10.1186/s12881-020-01038-6 |
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