Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants

Abstract Osteopetrosis is a genetically heterogenous, fatal bone disorder characterized by increased bone density. Globally, various genetic causes are reported for osteopetrosis with all forms of inheritance patterns. A precise molecular diagnosis is necessary for prognosis and for prescribing trea...

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Autores principales:	Chunyu Liu, Muhammad Ajmal, Zaineb Akram, Tariq Ghafoor, Muhammad Farhan, Sobia Shafique, Sughra Wahid, Shahar Bano, Jianqiu Xiao, Humayoon Shafique Satti, Feng Zhang, Tahir Naeem Khan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Autosomal recessive osteopetrosis Genetic diagnosis TCIRG1 Disease variants Internal medicine RC31-1245 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/2bf5b2c415524ca4aafc8083fa1e385f
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spelling	oai:doaj.org-article:2bf5b2c415524ca4aafc8083fa1e385f2021-11-14T12:07:42ZGenetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants10.1186/s12920-021-01117-41755-8794https://doaj.org/article/2bf5b2c415524ca4aafc8083fa1e385f2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01117-4https://doaj.org/toc/1755-8794Abstract Osteopetrosis is a genetically heterogenous, fatal bone disorder characterized by increased bone density. Globally, various genetic causes are reported for osteopetrosis with all forms of inheritance patterns. A precise molecular diagnosis is necessary for prognosis and for prescribing treatment paradigms in osteopetrosis. Here we report on thirteen individuals diagnosed with infantile malignant osteopetrosis coming from ten unrelated Pakistani families; nine of whom are consanguineous. We performed whole exome sequencing and Sanger sequencing in all families and identified homozygous variants in genes previously reported for autosomal recessive inheritance of osteopetrosis. All the identified variants are expected to affect the stability or length of gene products except one nonsynonymous missense variant. TCIRG1 was found as a candidate causal gene in majority of the families. We report six novel variants; four in TCIRG1 and one each in CLCN7 and OSTM1. Our combined findings will be helpful in molecular diagnosis and genetic counselling of patients with osteopetrosis particularly in populations with high consanguinity.Chunyu LiuMuhammad AjmalZaineb AkramTariq GhafoorMuhammad FarhanSobia ShafiqueSughra WahidShahar BanoJianqiu XiaoHumayoon Shafique SattiFeng ZhangTahir Naeem KhanBMCarticleAutosomal recessive osteopetrosisGenetic diagnosisTCIRG1Disease variantsInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Autosomal recessive osteopetrosis Genetic diagnosis TCIRG1 Disease variants Internal medicine RC31-1245 Genetics QH426-470
spellingShingle	Autosomal recessive osteopetrosis Genetic diagnosis TCIRG1 Disease variants Internal medicine RC31-1245 Genetics QH426-470 Chunyu Liu Muhammad Ajmal Zaineb Akram Tariq Ghafoor Muhammad Farhan Sobia Shafique Sughra Wahid Shahar Bano Jianqiu Xiao Humayoon Shafique Satti Feng Zhang Tahir Naeem Khan Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants
description	Abstract Osteopetrosis is a genetically heterogenous, fatal bone disorder characterized by increased bone density. Globally, various genetic causes are reported for osteopetrosis with all forms of inheritance patterns. A precise molecular diagnosis is necessary for prognosis and for prescribing treatment paradigms in osteopetrosis. Here we report on thirteen individuals diagnosed with infantile malignant osteopetrosis coming from ten unrelated Pakistani families; nine of whom are consanguineous. We performed whole exome sequencing and Sanger sequencing in all families and identified homozygous variants in genes previously reported for autosomal recessive inheritance of osteopetrosis. All the identified variants are expected to affect the stability or length of gene products except one nonsynonymous missense variant. TCIRG1 was found as a candidate causal gene in majority of the families. We report six novel variants; four in TCIRG1 and one each in CLCN7 and OSTM1. Our combined findings will be helpful in molecular diagnosis and genetic counselling of patients with osteopetrosis particularly in populations with high consanguinity.
format	article
author	Chunyu Liu Muhammad Ajmal Zaineb Akram Tariq Ghafoor Muhammad Farhan Sobia Shafique Sughra Wahid Shahar Bano Jianqiu Xiao Humayoon Shafique Satti Feng Zhang Tahir Naeem Khan
author_facet	Chunyu Liu Muhammad Ajmal Zaineb Akram Tariq Ghafoor Muhammad Farhan Sobia Shafique Sughra Wahid Shahar Bano Jianqiu Xiao Humayoon Shafique Satti Feng Zhang Tahir Naeem Khan
author_sort	Chunyu Liu
title	Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants
title_short	Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants
title_full	Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants
title_fullStr	Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants
title_full_unstemmed	Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants
title_sort	genetic analysis of osteopetrosis in pakistani families identifies novel and known sequence variants
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2bf5b2c415524ca4aafc8083fa1e385f
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Genetic analysis of osteopetrosis in Pakistani families identifies novel and known sequence variants

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