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Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis

BACKGROUND: Osteopetrosis is a rare form of skeletal dysplasia characterized by increased bone density that leads to bone marrow failure, compressive neuropathy, and skeletal dysmorphism. Molecular diagnosis is essential as it guides treatment and prognosis. We report Thai siblings with an ultra‐rar...

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Autores principales: Lertwilaiwittaya, Pongtawat, Suktitipat, Bhoom, Khongthon, Phongphak, Pongsapich, Warut, Limwongse, Chanin, Pithukpakorn, Manop
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372087/
https://www.ncbi.nlm.nih.gov/pubmed/34056870
http://dx.doi.org/10.1002/mgg3.1727
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author Lertwilaiwittaya, Pongtawat
Suktitipat, Bhoom
Khongthon, Phongphak
Pongsapich, Warut
Limwongse, Chanin
Pithukpakorn, Manop
author_facet Lertwilaiwittaya, Pongtawat
Suktitipat, Bhoom
Khongthon, Phongphak
Pongsapich, Warut
Limwongse, Chanin
Pithukpakorn, Manop
author_sort Lertwilaiwittaya, Pongtawat
collection PubMed
description BACKGROUND: Osteopetrosis is a rare form of skeletal dysplasia characterized by increased bone density that leads to bone marrow failure, compressive neuropathy, and skeletal dysmorphism. Molecular diagnosis is essential as it guides treatment and prognosis. We report Thai siblings with an ultra‐rare form of osteopetrosis. METHODS: The older brother and the younger sister presented with chronic mandibular osteomyelitis in their 20s. Since childhood, they had visual impairment, pathological fracture, and skeletal dysmorphism. Quadruplet whole‐exome sequencing was performed and confirmed with Sanger sequencing. Novel mutation in TNFSF11 (RANKL) c.842T>G, p.Phe281Cys was identified in a homozygous state in both siblings. RESULTS: Surgical debridement, antibiotic, and hyperbaric oxygen therapy were used and discontinued over a 6‐month period with normalization of C‐reactive protein. Hematopoietic stem cell transplantation candidacy was excluded by molecular diagnosis. CONCLUSION: We report a novel mutation in an ultra‐rare form of osteopetrosis. Our siblings manifested with a milder phenotype in comparison with nine cases previously published.
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spelling pubmed-83720872021-08-23 Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis Lertwilaiwittaya, Pongtawat Suktitipat, Bhoom Khongthon, Phongphak Pongsapich, Warut Limwongse, Chanin Pithukpakorn, Manop Mol Genet Genomic Med Original Articles BACKGROUND: Osteopetrosis is a rare form of skeletal dysplasia characterized by increased bone density that leads to bone marrow failure, compressive neuropathy, and skeletal dysmorphism. Molecular diagnosis is essential as it guides treatment and prognosis. We report Thai siblings with an ultra‐rare form of osteopetrosis. METHODS: The older brother and the younger sister presented with chronic mandibular osteomyelitis in their 20s. Since childhood, they had visual impairment, pathological fracture, and skeletal dysmorphism. Quadruplet whole‐exome sequencing was performed and confirmed with Sanger sequencing. Novel mutation in TNFSF11 (RANKL) c.842T>G, p.Phe281Cys was identified in a homozygous state in both siblings. RESULTS: Surgical debridement, antibiotic, and hyperbaric oxygen therapy were used and discontinued over a 6‐month period with normalization of C‐reactive protein. Hematopoietic stem cell transplantation candidacy was excluded by molecular diagnosis. CONCLUSION: We report a novel mutation in an ultra‐rare form of osteopetrosis. Our siblings manifested with a milder phenotype in comparison with nine cases previously published. John Wiley and Sons Inc. 2021-05-30 /pmc/articles/PMC8372087/ /pubmed/34056870 http://dx.doi.org/10.1002/mgg3.1727 Text en © 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Lertwilaiwittaya, Pongtawat
Suktitipat, Bhoom
Khongthon, Phongphak
Pongsapich, Warut
Limwongse, Chanin
Pithukpakorn, Manop
Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
title Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
title_full Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
title_fullStr Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
title_full_unstemmed Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
title_short Identification of novel mutation in RANKL by whole‐exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis
title_sort identification of novel mutation in rankl by whole‐exome sequencing in a thai family with osteopetrosis; a case report and review of rankl osteopetrosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372087/
https://www.ncbi.nlm.nih.gov/pubmed/34056870
http://dx.doi.org/10.1002/mgg3.1727
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