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Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia

Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone and/or dental mineralization, and decreased serum alkaline phosphatase (ALP) activity. ALPL, the only gene related with HPP, encodes tissue non-specific ALP (TNSALP). Few studies were carried out in ALPL gene mutatio...

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Autores principales: Xu, Lijun, Pang, Qianqian, Jiang, Yan, Wang, Ou, Li, Mei, Xing, Xiaoping, Xia, Weibo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131208/
https://www.ncbi.nlm.nih.gov/pubmed/29724887
http://dx.doi.org/10.1042/BSR20171377
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author Xu, Lijun
Pang, Qianqian
Jiang, Yan
Wang, Ou
Li, Mei
Xing, Xiaoping
Xia, Weibo
author_facet Xu, Lijun
Pang, Qianqian
Jiang, Yan
Wang, Ou
Li, Mei
Xing, Xiaoping
Xia, Weibo
author_sort Xu, Lijun
collection PubMed
description Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone and/or dental mineralization, and decreased serum alkaline phosphatase (ALP) activity. ALPL, the only gene related with HPP, encodes tissue non-specific ALP (TNSALP). Few studies were carried out in ALPL gene mutations in the Chinese population with HPP. The purpose of the present study is to elucidate the clinical and genetic characteristics of HPP in five unrelated Chinese families and two sporadic patients. Ten clinically diagnosed HPP patients from five unrelated Chinese families and two sporadic patients and fifty healthy controls were genetically investigated. All 12 exons and exon–intron boundaries of the ALPL gene were amplified by PCR and directly sequenced. The laboratory and radiological investigations were conducted simultaneously in these HPP ten patients. A 3D model of the TNSALP was used to predict the dominant negative effect of identified missense mutations. Three odonto, three childhood, and four adult types of HPP were clinically diagnosed. Ten mutations were identified in five unrelated Chinese families and two sporadic patients, including eight missense mutations and two frameshift mutations. Of which, four were novel: one frameshift mutation (p.R138Pfsx45); three missense mutations (p.C201R, p.V459A, p.C497S). No identical mutations and any other new ALPL mutations were found in unrelated 50 healthy controls. Our study demonstrated that the ALPL gene mutations are responsible for HPP in these Chinese families. These findings will be useful for clinicians to improve understanding of this heritable bone disorder.
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spelling pubmed-61312082018-09-12 Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia Xu, Lijun Pang, Qianqian Jiang, Yan Wang, Ou Li, Mei Xing, Xiaoping Xia, Weibo Biosci Rep Research Articles Hypophosphatasia (HPP) is a rare inherited disorder characterized by defective bone and/or dental mineralization, and decreased serum alkaline phosphatase (ALP) activity. ALPL, the only gene related with HPP, encodes tissue non-specific ALP (TNSALP). Few studies were carried out in ALPL gene mutations in the Chinese population with HPP. The purpose of the present study is to elucidate the clinical and genetic characteristics of HPP in five unrelated Chinese families and two sporadic patients. Ten clinically diagnosed HPP patients from five unrelated Chinese families and two sporadic patients and fifty healthy controls were genetically investigated. All 12 exons and exon–intron boundaries of the ALPL gene were amplified by PCR and directly sequenced. The laboratory and radiological investigations were conducted simultaneously in these HPP ten patients. A 3D model of the TNSALP was used to predict the dominant negative effect of identified missense mutations. Three odonto, three childhood, and four adult types of HPP were clinically diagnosed. Ten mutations were identified in five unrelated Chinese families and two sporadic patients, including eight missense mutations and two frameshift mutations. Of which, four were novel: one frameshift mutation (p.R138Pfsx45); three missense mutations (p.C201R, p.V459A, p.C497S). No identical mutations and any other new ALPL mutations were found in unrelated 50 healthy controls. Our study demonstrated that the ALPL gene mutations are responsible for HPP in these Chinese families. These findings will be useful for clinicians to improve understanding of this heritable bone disorder. Portland Press Ltd. 2018-08-29 /pmc/articles/PMC6131208/ /pubmed/29724887 http://dx.doi.org/10.1042/BSR20171377 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Xu, Lijun
Pang, Qianqian
Jiang, Yan
Wang, Ou
Li, Mei
Xing, Xiaoping
Xia, Weibo
Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
title Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
title_full Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
title_fullStr Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
title_full_unstemmed Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
title_short Four novel mutations in the ALPL gene in Chinese patients with odonto, childhood, and adult hypophosphatasia
title_sort four novel mutations in the alpl gene in chinese patients with odonto, childhood, and adult hypophosphatasia
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131208/
https://www.ncbi.nlm.nih.gov/pubmed/29724887
http://dx.doi.org/10.1042/BSR20171377
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