Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing. / Gul, Rutaba; Firasat, Sabika; Schubert, Mikkel; Ullah, Asmat; Peña, Elionora; Thuesen, Anne C.B.; Hussain, Mulazim; Staeger, Frederik F.; Gjesing, Anette P.; Albrechtsen, Anders; Hansen, Torben.
In: Frontiers in Genetics, Vol. 14, 1128850, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Identifying the genetic causes of phenotypically diagnosed Pakistani mucopolysaccharidoses patients by whole genome sequencing
AU - Gul, Rutaba
AU - Firasat, Sabika
AU - Schubert, Mikkel
AU - Ullah, Asmat
AU - Peña, Elionora
AU - Thuesen, Anne C.B.
AU - Hussain, Mulazim
AU - Staeger, Frederik F.
AU - Gjesing, Anette P.
AU - Albrechtsen, Anders
AU - Hansen, Torben
N1 - Publisher Copyright: Copyright © 2023 Gul, Firasat, Schubert, Ullah, Peña, Thuesen, Hussain, Staeger, Gjesing, Albrechtsen and Hansen.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - ABCA5
KW - lysosomal storage disorder
KW - mucopolysaccharidosis
KW - Pakistani families
KW - whole genome sequencing
U2 - 10.3389/fgene.2023.1128850
DO - 10.3389/fgene.2023.1128850
M3 - Journal article
C2 - 37091798
AN - SCOPUS:85153064328
VL - 14
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 1128850
ER -
ID: 345645562