Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing
Background: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases, which encompass more than 50 different subtypes of pathologies. These disorders are caused by defects in lysosomal enzymes, transporters, and other non-lysosomal proteins. Mucopolysaccharidosis (MPS) is the m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1128850/full |
| _version_ | 1797852133225136128 |
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| author | Rutaba Gul Rutaba Gul Sabika Firasat Mikkel Schubert Asmat Ullah Elionora Peña Anne C. B. Thuesen Mulazim Hussain Frederik F. Staeger Anette P. Gjesing Anders Albrechtsen Torben Hansen |
| author_facet | Rutaba Gul Rutaba Gul Sabika Firasat Mikkel Schubert Asmat Ullah Elionora Peña Anne C. B. Thuesen Mulazim Hussain Frederik F. Staeger Anette P. Gjesing Anders Albrechtsen Torben Hansen |
| author_sort | Rutaba Gul |
| collection | DOAJ |
| description | Background: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases, which encompass more than 50 different subtypes of pathologies. These disorders are caused by defects in lysosomal enzymes, transporters, and other non-lysosomal proteins. Mucopolysaccharidosis (MPS) is the most common subgroup of lysosomal storage disorders in which the body is unable to properly breakdown mucopolysaccharides. The aim of the present study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II.Methods: Clinical diagnosis identified 12 with mucopolysaccharidosis I and 2 with mucopolysaccharidosis II in 14 families and whole genome sequencing (WGS) was performed to identify the causative variations in 15 affected individuals. Twenty-two unaffected individuals including parents or normal siblings of patients were also sequenced. Putative causal variants were identified by co-segregation and functional annotation.Results: Analysis of whole genome sequencing data revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes (IDUA, GALNS, SGSH, GAA, IDS, ALDOB, TRAPPC4, MASP1, SMARCAL, KIAA1109, HERC1, RRAS2) and a novel candidate gene (ABCA5) for lysosomal storage disorder-like phenotypes, which has previously been associated with symptoms strongly related with lysosomal storage disorder in animal models.Conclusion: Multigenic inheritance was found in several families highlighting the importance of searching for homozygous pathogenic variants in several genes also in families with a high degree of consanguinity. |
| first_indexed | 2024-04-09T19:29:13Z |
| format | Article |
| id | doaj.art-b7361e4010c94f559237093e8ab44814 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-09T19:29:13Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-b7361e4010c94f559237093e8ab448142023-04-05T05:28:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-04-011410.3389/fgene.2023.11288501128850Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencingRutaba Gul0Rutaba Gul1Sabika Firasat2Mikkel Schubert3Asmat Ullah4Elionora Peña5Anne C. B. Thuesen6Mulazim Hussain7Frederik F. Staeger8Anette P. Gjesing9Anders Albrechtsen10Torben Hansen11Department of Zoology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, PakistanNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkDepartment of Zoology, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, PakistanNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkThe Children Hospital, Pakistan Institute of Medical Sciences (PIMS), Islamabad, PakistanSection for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkSection for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkBackground: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases, which encompass more than 50 different subtypes of pathologies. These disorders are caused by defects in lysosomal enzymes, transporters, and other non-lysosomal proteins. Mucopolysaccharidosis (MPS) is the most common subgroup of lysosomal storage disorders in which the body is unable to properly breakdown mucopolysaccharides. The aim of the present study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II.Methods: Clinical diagnosis identified 12 with mucopolysaccharidosis I and 2 with mucopolysaccharidosis II in 14 families and whole genome sequencing (WGS) was performed to identify the causative variations in 15 affected individuals. Twenty-two unaffected individuals including parents or normal siblings of patients were also sequenced. Putative causal variants were identified by co-segregation and functional annotation.Results: Analysis of whole genome sequencing data revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes (IDUA, GALNS, SGSH, GAA, IDS, ALDOB, TRAPPC4, MASP1, SMARCAL, KIAA1109, HERC1, RRAS2) and a novel candidate gene (ABCA5) for lysosomal storage disorder-like phenotypes, which has previously been associated with symptoms strongly related with lysosomal storage disorder in animal models.Conclusion: Multigenic inheritance was found in several families highlighting the importance of searching for homozygous pathogenic variants in several genes also in families with a high degree of consanguinity.https://www.frontiersin.org/articles/10.3389/fgene.2023.1128850/fulllysosomal storage disordermucopolysaccharidosisPakistani familieswhole genome sequencingABCA5 |
| spellingShingle | Rutaba Gul Rutaba Gul Sabika Firasat Mikkel Schubert Asmat Ullah Elionora Peña Anne C. B. Thuesen Mulazim Hussain Frederik F. Staeger Anette P. Gjesing Anders Albrechtsen Torben Hansen Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing Frontiers in Genetics lysosomal storage disorder mucopolysaccharidosis Pakistani families whole genome sequencing ABCA5 |
| title | Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing |
| title_full | Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing |
| title_fullStr | Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing |
| title_full_unstemmed | Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing |
| title_short | Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing |
| title_sort | identifying the genetic causes of phenotypically diagnosed pakistani mucopolysaccharidoses patients by whole genome sequencing |
| topic | lysosomal storage disorder mucopolysaccharidosis Pakistani families whole genome sequencing ABCA5 |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1128850/full |
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