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Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families

BACKGROUND: Retinitis Pigmentosa (RP) is a clinically and genetically progressive retinal dystrophy associated with severe visual impairments and sometimes blindness, the most common syndromic form of which is Usher syndrome (USH). This study aimed to further increase understanding of the spectrum o...

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Autores principales: Marwan, Muhammad, Dawood, Muhammad, Ullah, Mukhtar, Shah, Irfan Ullah, Khan, Niamat, Hassan, Muhammad Taimur, Karam, Muhammad, Rawlins, Lettie E., Baple, Emma L, Crosby, Andrew H., Saleha, Shamim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170854/
https://www.ncbi.nlm.nih.gov/pubmed/37165311
http://dx.doi.org/10.1186/s12886-023-02948-8
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author Marwan, Muhammad
Dawood, Muhammad
Ullah, Mukhtar
Shah, Irfan Ullah
Khan, Niamat
Hassan, Muhammad Taimur
Karam, Muhammad
Rawlins, Lettie E.
Baple, Emma L
Crosby, Andrew H.
Saleha, Shamim
author_facet Marwan, Muhammad
Dawood, Muhammad
Ullah, Mukhtar
Shah, Irfan Ullah
Khan, Niamat
Hassan, Muhammad Taimur
Karam, Muhammad
Rawlins, Lettie E.
Baple, Emma L
Crosby, Andrew H.
Saleha, Shamim
author_sort Marwan, Muhammad
collection PubMed
description BACKGROUND: Retinitis Pigmentosa (RP) is a clinically and genetically progressive retinal dystrophy associated with severe visual impairments and sometimes blindness, the most common syndromic form of which is Usher syndrome (USH). This study aimed to further increase understanding of the spectrum of RP in the Khyber Pakhtunkhwa region of Pakistan. METHODOLOGY: Four consanguineous families of Pashtun ethnic group were investigated which were referred by the local collaborating ophthalmologists. In total 42 individuals in four families were recruited and investigated using whole exome and dideoxy sequencing. Among them, 20 were affected individuals including 6 in both family 1 and 2, 5 in family 3 and 3 in family 4. RESULT: Pathogenic gene variants were identified in all four families, including two in cone dystrophy and RP genes in the same family (PDE6C; c.480delG, p.Asn161ThrfsTer33 and TULP1; c.238 C > T, p.Gln80Ter) with double-homozygous individuals presenting with more severe disease. Other pathogenic variants were identified in MERTK (c.2194C > T, p.Arg732Ter), RHO (c.448G > A, p.Glu150Lys) associated with non-syndromic RP, and MYO7A (c.487G > A, p.Gly163Arg) associated with USH. In addition, the reported variants were of clinical significance as the PDE6C variant was detected novel, whereas TULP1, MERTK, and MYO7A variants were detected rare and first time found segregating with retinal dystrophies in Pakistani consanguineous families. CONCLUSIONS: This study increases knowledge of the genetic basis of retinal dystrophies in families from Pakistan providing information important for genetic testing and diagnostic provision particularly from the Khyber Pakhtunkhwa region. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-023-02948-8.
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spelling pubmed-101708542023-05-11 Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families Marwan, Muhammad Dawood, Muhammad Ullah, Mukhtar Shah, Irfan Ullah Khan, Niamat Hassan, Muhammad Taimur Karam, Muhammad Rawlins, Lettie E. Baple, Emma L Crosby, Andrew H. Saleha, Shamim BMC Ophthalmol Research BACKGROUND: Retinitis Pigmentosa (RP) is a clinically and genetically progressive retinal dystrophy associated with severe visual impairments and sometimes blindness, the most common syndromic form of which is Usher syndrome (USH). This study aimed to further increase understanding of the spectrum of RP in the Khyber Pakhtunkhwa region of Pakistan. METHODOLOGY: Four consanguineous families of Pashtun ethnic group were investigated which were referred by the local collaborating ophthalmologists. In total 42 individuals in four families were recruited and investigated using whole exome and dideoxy sequencing. Among them, 20 were affected individuals including 6 in both family 1 and 2, 5 in family 3 and 3 in family 4. RESULT: Pathogenic gene variants were identified in all four families, including two in cone dystrophy and RP genes in the same family (PDE6C; c.480delG, p.Asn161ThrfsTer33 and TULP1; c.238 C > T, p.Gln80Ter) with double-homozygous individuals presenting with more severe disease. Other pathogenic variants were identified in MERTK (c.2194C > T, p.Arg732Ter), RHO (c.448G > A, p.Glu150Lys) associated with non-syndromic RP, and MYO7A (c.487G > A, p.Gly163Arg) associated with USH. In addition, the reported variants were of clinical significance as the PDE6C variant was detected novel, whereas TULP1, MERTK, and MYO7A variants were detected rare and first time found segregating with retinal dystrophies in Pakistani consanguineous families. CONCLUSIONS: This study increases knowledge of the genetic basis of retinal dystrophies in families from Pakistan providing information important for genetic testing and diagnostic provision particularly from the Khyber Pakhtunkhwa region. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-023-02948-8. BioMed Central 2023-05-10 /pmc/articles/PMC10170854/ /pubmed/37165311 http://dx.doi.org/10.1186/s12886-023-02948-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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
Marwan, Muhammad
Dawood, Muhammad
Ullah, Mukhtar
Shah, Irfan Ullah
Khan, Niamat
Hassan, Muhammad Taimur
Karam, Muhammad
Rawlins, Lettie E.
Baple, Emma L
Crosby, Andrew H.
Saleha, Shamim
Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families
title Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families
title_full Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families
title_fullStr Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families
title_full_unstemmed Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families
title_short Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families
title_sort unravelling the genetic basis of retinal dystrophies in pakistani consanguineous families
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10170854/
https://www.ncbi.nlm.nih.gov/pubmed/37165311
http://dx.doi.org/10.1186/s12886-023-02948-8
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