Back to Search
Start Over
Lysosomal storage disorders: Novel and frequent pathogenic variants in a large cohort of Indian patients of Pompe, Fabry, Gaucher and Hurler disease.
- Source :
-
Clinical biochemistry [Clin Biochem] 2021 Mar; Vol. 89, pp. 14-37. Date of Electronic Publication: 2020 Dec 08. - Publication Year :
- 2021
-
Abstract
- Objectives: Diagnosis of lysosomal storage disorders (LSDs) remains challenging due to wide clinical, biochemical and molecular heterogeneity. The study applies a combined biochemical and genetic approach to diagnose symptomatic Indian patients of Pompe, Fabry, Gaucher and Hurler disease to generate a comprehensive dataset of pathogenic variants for these disorders.<br />Design & Methods: Symptomatic patients were biochemically diagnosed by fluorometric methods and molecular confirmation was carried out by gene sequencing. Genetic variants were analyzed according to the ACMG/AMP 2015 variant interpretation guidelines.<br />Results: Amongst the 2181 suspected patients, 285 (13%) were biochemically diagnosed. Of these, 22.5% (64/285) diagnosed with Pompe disease harboured c.1933G>A, c.1A>G, c.1927G>A and c.2783G>C as common and 10 novel pathogenic variants while 7.4% (21/285) patients diagnosed with Fabry disease carried c.851T>C, c.902G>A, c.905A>C and c.1212&#95;1234del as frequent disease-causing variants along with 7 novel pathogenic variants. As many as 48.4% (138/285) patients were diagnosed with Gaucher disease and had c.1448T>C as the most common pathogenic variant followed by c.1342G>C and c.754T>C with 7 previously unreported disease-causing variants and in the 21.7% (62/285) diagnosed cases of Hurler disease, c.1469T>C, c.754delC c.568&#95;581del and c.1898C>T were identified as the most common causative variants along with 21 novel pathogenic variants.<br />Conclusion: This comprehensive data set of disease-causing frequent and novel pathogenic variants reported for the first time in such a large patient cohort for each of these four LSDs from the Indian sub-continent, along with their biochemical and clinical spectrum will contribute towards providing definitive diagnosis and treatment, identifying carrier status, as well as in counselling prenatal cases to reduce the morbidity and mortality associated with these disorders.<br /> (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Child
Child, Preschool
Cohort Studies
Fabry Disease pathology
Female
Gaucher Disease pathology
Glycogen Storage Disease Type II pathology
Humans
Infant
Infant, Newborn
Lysosomes
Male
Middle Aged
Mucopolysaccharidosis I pathology
Young Adult
Biomarkers analysis
Fabry Disease genetics
Gaucher Disease genetics
Glycogen Storage Disease Type II genetics
Glycoproteins genetics
Mucopolysaccharidosis I genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2933
- Volume :
- 89
- Database :
- MEDLINE
- Journal :
- Clinical biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33301762
- Full Text :
- https://doi.org/10.1016/j.clinbiochem.2020.12.002