Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing. / Gul, Rutaba; Firasat, Sabika; Schubert, Mikkel; Ullah, Asmat; Peña, Elionora; Thuesen, Anne C.B.; Gjesing, Annete P.; Hussain, Mulazim; Tufail, Muhammad; Saqib, Muhammad; Afshan, Kiran; Hansen, Torben.

In: Frontiers in Genetics, Vol. 14, 1254909, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gul, R, Firasat, S, Schubert, M, Ullah, A, Peña, E, Thuesen, ACB, Gjesing, AP, Hussain, M, Tufail, M, Saqib, M, Afshan, K & Hansen, T 2023, 'Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing', Frontiers in Genetics, vol. 14, 1254909. https://doi.org/10.3389/fgene.2023.1254909

APA

Gul, R., Firasat, S., Schubert, M., Ullah, A., Peña, E., Thuesen, A. C. B., Gjesing, A. P., Hussain, M., Tufail, M., Saqib, M., Afshan, K., & Hansen, T. (2023). Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing. Frontiers in Genetics, 14, [1254909]. https://doi.org/10.3389/fgene.2023.1254909

Vancouver

Gul R, Firasat S, Schubert M, Ullah A, Peña E, Thuesen ACB et al. Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing. Frontiers in Genetics. 2023;14. 1254909. https://doi.org/10.3389/fgene.2023.1254909

Author

Gul, Rutaba ; Firasat, Sabika ; Schubert, Mikkel ; Ullah, Asmat ; Peña, Elionora ; Thuesen, Anne C.B. ; Gjesing, Annete P. ; Hussain, Mulazim ; Tufail, Muhammad ; Saqib, Muhammad ; Afshan, Kiran ; Hansen, Torben. / Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing. In: Frontiers in Genetics. 2023 ; Vol. 14.

Bibtex

@article{e969450557524d5893e667ef71b00df7,
title = "Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing",
abstract = "Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs are caused by excessive accumulation of mucopolysaccharides due to missing or deficiency of enzymes required for the degradation of specific macromolecules. MPS I-IV, MPS VI, MPS VII, and MPS IX are sub-types of mucopolysaccharidoses. Among these, MPS III (also known as Sanfilippo) and MPS IV (Morquio) syndromes are lethal and prevalent sub-types. This study aimed to identify causal genetic variants in cases of MPS III and MPS IV and characterize genotype-phenotype relations in Pakistan. We performed clinical, biochemical and genetic analysis using Whole Genome Sequencing (WGS) in 14 Pakistani families affected with MPS III or MPS IV. Patients were classified into MPS III by history of aggressive behaviors, dementia, clear cornea and into MPS IV by short trunk, short stature, reversed ratio of upper segment to lower segment with a short upper segment. Data analysis and variant selections were made based on segregation analysis, examination of known MPS III and MPS IV genes, gene function, gene expression, the pathogenicity of variants based on ACMG guidelines and in silico analysis. In total, 58 individuals from 14 families were included in the present study. Six families were clinically diagnosed with MPS III and eight families with MPS IV. WGS revealed variants in MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG as well as the genes VWA3B, BTD, and GNPTG which have not previously associated with MPS. One family had causal variants in both GALNS and BTD. Accurate and early diagnosis of MPS in children represents a helpful step for designing therapeutic strategies to protect different organs from permanent damage. In addition, pre-natal screening and identification of genetic etiology will facilitate genetic counselling of the affected families. Identification of novel causal MPS genes might help identifying new targeted therapies to treat LSDs.",
keywords = "Morquio syndrome, Pakistani families, Sanfilippo syndrome, VWA3B, whole genome sequencing",
author = "Rutaba Gul and Sabika Firasat and Mikkel Schubert and Asmat Ullah and Elionora Pe{\~n}a and Thuesen, {Anne C.B.} and Gjesing, {Annete P.} and Mulazim Hussain and Muhammad Tufail and Muhammad Saqib and Kiran Afshan and Torben Hansen",
note = "Publisher Copyright: Copyright {\textcopyright} 2023 Gul, Firasat, Schubert, Ullah, Pe{\~n}a, Thuesen, Gjesing, Hussain, Tufail, Saqib, Afshan and Hansen.",
year = "2023",
doi = "10.3389/fgene.2023.1254909",
language = "English",
volume = "14",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Identification of genetic variants associated with a wide spectrum of phenotypes clinically diagnosed as Sanfilippo and Morquio syndromes using whole genome sequencing

AU - Gul, Rutaba

AU - Firasat, Sabika

AU - Schubert, Mikkel

AU - Ullah, Asmat

AU - Peña, Elionora

AU - Thuesen, Anne C.B.

AU - Gjesing, Annete P.

AU - Hussain, Mulazim

AU - Tufail, Muhammad

AU - Saqib, Muhammad

AU - Afshan, Kiran

AU - Hansen, Torben

N1 - Publisher Copyright: Copyright © 2023 Gul, Firasat, Schubert, Ullah, Peña, Thuesen, Gjesing, Hussain, Tufail, Saqib, Afshan and Hansen.

PY - 2023

Y1 - 2023

N2 - Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs are caused by excessive accumulation of mucopolysaccharides due to missing or deficiency of enzymes required for the degradation of specific macromolecules. MPS I-IV, MPS VI, MPS VII, and MPS IX are sub-types of mucopolysaccharidoses. Among these, MPS III (also known as Sanfilippo) and MPS IV (Morquio) syndromes are lethal and prevalent sub-types. This study aimed to identify causal genetic variants in cases of MPS III and MPS IV and characterize genotype-phenotype relations in Pakistan. We performed clinical, biochemical and genetic analysis using Whole Genome Sequencing (WGS) in 14 Pakistani families affected with MPS III or MPS IV. Patients were classified into MPS III by history of aggressive behaviors, dementia, clear cornea and into MPS IV by short trunk, short stature, reversed ratio of upper segment to lower segment with a short upper segment. Data analysis and variant selections were made based on segregation analysis, examination of known MPS III and MPS IV genes, gene function, gene expression, the pathogenicity of variants based on ACMG guidelines and in silico analysis. In total, 58 individuals from 14 families were included in the present study. Six families were clinically diagnosed with MPS III and eight families with MPS IV. WGS revealed variants in MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG as well as the genes VWA3B, BTD, and GNPTG which have not previously associated with MPS. One family had causal variants in both GALNS and BTD. Accurate and early diagnosis of MPS in children represents a helpful step for designing therapeutic strategies to protect different organs from permanent damage. In addition, pre-natal screening and identification of genetic etiology will facilitate genetic counselling of the affected families. Identification of novel causal MPS genes might help identifying new targeted therapies to treat LSDs.

AB - Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs are caused by excessive accumulation of mucopolysaccharides due to missing or deficiency of enzymes required for the degradation of specific macromolecules. MPS I-IV, MPS VI, MPS VII, and MPS IX are sub-types of mucopolysaccharidoses. Among these, MPS III (also known as Sanfilippo) and MPS IV (Morquio) syndromes are lethal and prevalent sub-types. This study aimed to identify causal genetic variants in cases of MPS III and MPS IV and characterize genotype-phenotype relations in Pakistan. We performed clinical, biochemical and genetic analysis using Whole Genome Sequencing (WGS) in 14 Pakistani families affected with MPS III or MPS IV. Patients were classified into MPS III by history of aggressive behaviors, dementia, clear cornea and into MPS IV by short trunk, short stature, reversed ratio of upper segment to lower segment with a short upper segment. Data analysis and variant selections were made based on segregation analysis, examination of known MPS III and MPS IV genes, gene function, gene expression, the pathogenicity of variants based on ACMG guidelines and in silico analysis. In total, 58 individuals from 14 families were included in the present study. Six families were clinically diagnosed with MPS III and eight families with MPS IV. WGS revealed variants in MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG as well as the genes VWA3B, BTD, and GNPTG which have not previously associated with MPS. One family had causal variants in both GALNS and BTD. Accurate and early diagnosis of MPS in children represents a helpful step for designing therapeutic strategies to protect different organs from permanent damage. In addition, pre-natal screening and identification of genetic etiology will facilitate genetic counselling of the affected families. Identification of novel causal MPS genes might help identifying new targeted therapies to treat LSDs.

KW - Morquio syndrome

KW - Pakistani families

KW - Sanfilippo syndrome

KW - VWA3B

KW - whole genome sequencing

U2 - 10.3389/fgene.2023.1254909

DO - 10.3389/fgene.2023.1254909

M3 - Journal article

C2 - 37772257

AN - SCOPUS:85172018431

VL - 14

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 1254909

ER -

ID: 369085348