Mutational spectrum associated with oculocutaneous albinism and Hermansky-Pudlak syndrome in nine Pakistani families.
Humans
Albinism, Oculocutaneous
/ genetics
Pakistan
Female
Male
Hermanski-Pudlak Syndrome
/ genetics
Pedigree
Mutation
Exome Sequencing
Child
Adult
Adolescent
DNA Mutational Analysis
Monophenol Monooxygenase
/ genetics
Child, Preschool
Membrane Transport Proteins
/ genetics
Young Adult
Membrane Proteins
HPS1
OCA2
TYR
Exome sequencing
Nystagmus
Oculocutaneous albinism
Pakistan
Journal
BMC ophthalmology
ISSN: 1471-2415
Titre abrégé: BMC Ophthalmol
Pays: England
ID NLM: 100967802
Informations de publication
Date de publication:
14 Aug 2024
14 Aug 2024
Historique:
received:
29
06
2023
accepted:
20
11
2023
medline:
15
8
2024
pubmed:
15
8
2024
entrez:
14
8
2024
Statut:
epublish
Résumé
Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition. Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software. WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1. Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.
Sections du résumé
BACKGROUND
BACKGROUND
Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition.
METHODS
METHODS
Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software.
RESULTS
RESULTS
WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1.
CONCLUSIONS
CONCLUSIONS
Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.
Identifiants
pubmed: 39143519
doi: 10.1186/s12886-024-03611-6
pii: 10.1186/s12886-024-03611-6
doi:
Substances chimiques
HPS1 protein, human
0
OCA2 protein, human
0
Monophenol Monooxygenase
EC 1.14.18.1
Membrane Transport Proteins
0
Membrane Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
345Informations de copyright
© 2024. The Author(s).
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