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Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis
- Source :
- Molecular Therapy-Methods and Clinical Development, 17, 337-348. Cell Press, Molecular Therapy: Methods & Clinical Development, Vol 17, Iss, Pp 337-348 (2020), Molecular therapy-Methods & clinical development, 17, 337-348. CELL PRESS
- Publication Year :
- 2020
- Publisher :
- CELL PRESS, 2020.
-
Abstract
- Pompe disease is a metabolic disorder caused by a deficiency of the glycogen-hydrolyzing lysosomal enzyme acid α-glucosidase (GAA), which leads to progressive muscle wasting. This autosomal-recessive disorder is the result of disease-associated variants located in the GAA gene. In the present study, we performed extended molecular diagnostic analysis to identify novel disease-associated variants in six suspected Pompe patients from four different families for which conventional diagnostic assays were insufficient. Additional assays, such as a generic-splicing assay, minigene analysis, SNP array analysis, and targeted Sanger sequencing, allowed the identification of an exonic deletion, a promoter deletion, and a novel splicing variant located in the 5' UTR. Furthermore, we describe the diagnostic process for an infantile patient with an atypical phenotype, consisting of left ventricular hypertrophy but no signs of muscle weakness or motor problems. This led to the identification of a genetic mosaicism for a very severe GAA variant caused by a segmental uniparental isodisomy (UPD). With this study, we aim to emphasize the need for additional analyses to detect new disease-associated GAA variants and non-Mendelian genotypes in Pompe disease where conventional DNA diagnostic assays are insufficient. ispartof: MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT vol:17 pages:337-348 ispartof: location:United States status: published
- Subjects :
- 0301 basic medicine
lcsh:QH426-470
UNIPARENTAL DISOMY
THERAPY
EXON INCLUSION
03 medical and health sciences
symbols.namesake
0302 clinical medicine
Genotype
Glycogen storage disease type II
Genetics
medicine
diagnostics
lcsh:QH573-671
Molecular Biology
Gene
Sanger sequencing
COMPLEX
business.industry
lcsh:Cytology
DELETION
Metabolic disorder
Pompe disease
medicine.disease
ALPHA-GLUCOSIDASE
segmental uniparental isodisomy
Uniparental disomy
lcsh:Genetics
030104 developmental biology
mosaicism
Uniparental Isodisomy
glycogen storage disease type II
030220 oncology & carcinogenesis
HUMAN GENE MUTATION
symbols
Molecular Medicine
business
Minigene
Subjects
Details
- Language :
- English
- ISSN :
- 23290501
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Molecular therapy-Methods & clinical development
- Accession number :
- edsair.doi.dedup.....e7ecb78b1b70d26d2f28c85fc9157510