Glycogen storage disease type II: identification of a dinucleotide deletion and a common missense mutation in the lysosomal α‐glucosidase gene

Ma, Kroos; D, van Leenen; Verbiest, J. R.; Aj, Reuser; Mm, Hermans

doi:10.1111/j.1399-0004.1998.tb02749.x

Cited by 18 publications

(7 citation statements)

References 9 publications

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“…This variant is associated with the classic infantile phenotype when combined with a null allele. 25,26 Sanger sequence analysis of the parents (both showed no signs of Pompe disease) found the c.925G>A only in a heterozygous state in paternal DNA. No other disease-associated variants were identified in the patient nor in his parents (Table 2).…”

Section: Patientmentioning

confidence: 99%

Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis

Groen

Faria

Iuliano

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Pompe disease is a metabolic disorder caused by a deficiency of the glycogen-hydrolyzing lysosomal enzyme acid a-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 0 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.

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Section: Patientmentioning

confidence: 99%

Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis

Groen

Faria

Iuliano

et al. 2020

Molecular Therapy - Methods & Clinical Development

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“…These are c.525delT, c.925G> A (p.Gly309Arg), c.1655T> C (p.Leu552Pro), c.2237G> A (p.Trp746X), c.1076-1G> C (r.0?) and the deletion of exon 18 (c.2481 + 102_2646 + 31del) [64,[69][70][71][72][73][74][75][76]. All the latter mutations are severe as they are associated with classic-infantile Pompe disease in homozygous or compound heterozygous state.…”

Section: Bloodspots and Newborn Screeningmentioning

confidence: 99%

Enzymatic and molecular strategies to diagnose Pompe disease

Reuser

Verheijen

Kroos

et al. 2009

Expert Opinion on Medical Diagnostics

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Enzyme replacement therapy for Pompe disease, a neuromuscular disorder characterized by lysosomal glycogen storage due to acid α-glucosidase deficiency, has entered the clinic. There is more than ever a need for early and reliable diagnosis. The objective of this review is to present a critical review of the recent literature on laboratory procedures to diagnose Pompe disease by enzymatic assay and DNA analysis. The methods we used were Compilation and expert interpretation of recent and relevant publications. The introduction of new and the updating of existing laboratory procedures have facilitated the diagnosis of Pompe disease (glycogen storage disease type II; acid maltase deficiency; OMIM 232300). With regard to enzymatic analysis, the application of acarbose as inhibitor of maltase-glucoamylase has enabled the use of mixed leukocyte preparations as diagnostic material. The use of glycogen as a natural substrate in the reaction mixture adds to the selectivity of this procedure. Newborn screening is envisaged and facilitated by the introduction of high-throughput procedures. DNA analysis has become an integral part of the diagnostic procedure for confirmation and completion, for carrier detection, and for genetic counseling.

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“…In the IOPD patients, this variant was combined with the c.-32-13 T > G and the c.875 A > G (p.Tyr292Cys) (rs1057516600) disease-causing variants and an early (age 3-4.5 months) disease manifestation. Analysis of Arg600His transfected COS-7 cells demonstrated less than 2% residual GAA enzyme activity compared to wild-type controls [34]. Relatively low GAA enzyme activity has also been found in patient six (P6) with c.-32-13 T > G/c.307 T > G genotype (Table 1; Figure 1A,B).…”

Section: Discussionmentioning

confidence: 82%

“…The c.925G > A (p.Gly309Arg) variant has been reported in at least five patients with Pompe disease [36,51,52]. Expressed in COS-7 cells, this variant did not produce a decreased GAA activity and showed evidence of abnormal processing [34,53]. The c.1468 T > C (p.Phe490Leu) alteration is currently not reported in some of the public databases such as ClinVar or HGMD.…”

Section: Discussionmentioning

confidence: 99%

Correlation of GAA Genotype and Acid-α-Glucosidase Enzyme Activity in Hungarian Patients with Pompe Disease

Gál

Grosz

Borsos

et al. 2021

Life

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Pompe disease is caused by the accumulation of glycogen in the lysosomes due to a deficiency of the lysosomal acid-α-glucosidase (GAA) enzyme. Depending on residual enzyme activity, the disease manifests two distinct phenotypes. In this study, we assess an enzymatic and genetic analysis of Hungarian patients with Pompe disease. Twenty-four patients diagnosed with Pompe disease were included. Enzyme activity of acid-α-glucosidase was measured by mass spectrometry. Sanger sequencing and an MLPA of the GAA gene were performed in all patients. Twenty (83.33%) patients were classified as having late-onset Pompe disease and four (16.66%) had infantile-onset Pompe disease. Fifteen different pathogenic GAA variants were detected. The most common finding was the c.-32-13 T > G splice site alteration. Comparing the α-glucosidase enzyme activity of homozygous cases to the compound heterozygous cases of the c.-32-13 T > G disease-causing variant, the mean GAA activity in homozygous cases was significantly higher. The lowest enzyme activity was found in cases where the c.-32-13 T > G variant was not present. The localization of the identified sequence variations in regions encoding the crucial protein domains of GAA correlates with severe effects on enzyme activity. A better understanding of the impact of pathogenic gene variations may help earlier initiation of enzyme replacement therapy (ERT) if subtle symptoms occur. Further information on the effect of GAA gene variation on the efficacy of treatment and the extent of immune response to ERT would be of importance for optimal disease management and designing effective treatment plans.

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Glycogen storage disease type II: identification of a dinucleotide deletion and a common missense mutation in the lysosomal α‐glucosidase gene

Cited by 18 publications

References 9 publications

Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis

Novel GAA Variants and Mosaicism in Pompe Disease Identified by Extended Analyses of Patients with an Incomplete DNA Diagnosis

Enzymatic and molecular strategies to diagnose Pompe disease

Correlation of GAA Genotype and Acid-α-Glucosidase Enzyme Activity in Hungarian Patients with Pompe Disease

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