Identification of two novel variants in GAA underlying infantile-onset Pompe disease in two Pakistani families
-
Aman Ullah
,
Bibi Zubaida
Abstract
Background
Pompe disease (PD) is an autosomal recessive metabolic myopathy with an average incidence of one in 40,000 live births. It has a variable age of onset and can be diagnosed within the first 3 months. Heart involvement and muscle weakness are its primary manifestations.
Case presentation
We describe two families affected by PD with two rare, novel variants. To date, pathogenic variants in acid α-glucosidase (GAA) alone have accounted for all cases of the disease. Both families were screened for pathogenic sequence variations. This study presents the implications of regulatory or modifier sequences in the disease pathogenesis for the first time. A homozygous missense p.Arg854Gln variant in family A and a single heterozygous variant (p.Asn925His) in family B were found to be segregating according to the disease phenotype. The variants were not detected in our in-house database comprising 50 whole-exome sequences of healthy individuals from a local unrelated Pakistani population. In silico analyses predicted that the variants would have deleterious effects on the protein structure.
Conclusions
The variants likely underlie the infantile-onset PD (IOPD) in these Pakistani families. The study expands the mutation spectrum of GAA associated with IOPD and highlights the insufficiency of screening the GAA coding sequence to determine the cause of IOPD. The work should be helpful in carrier identification, improving genetic counselling, and prenatal diagnosis.
Acknowledgements
Aman Ullah was supported by the Higher Education Commission of Pakistan through the Indigenous PhD Fellowship (PIN: 213-56956-2BM2-133).
Author contributions: All of the authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
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©2020 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
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Artikel in diesem Heft
- Frontmatter
- Review
- Prevalence of obesity and overweight in Iranian students: a systematic review and meta-analysis
- Original Articles
- Trends in pediatric obesity management, a survey from the Pediatric Endocrine Society Obesity Committee
- Utility of MR proton density fat fraction and its correlation with ultrasonography and biochemical markers in nonalcoholic fatty liver disease in overweight adolescents
- Vitamin D status and its relation to insulin resistance in a Mexican pediatric population
- Elevated serum uric acid, hyperuricaemia and dietary patterns among adolescents in mainland China
- Is there a relationship between the dietary inflammatory index and metabolic syndrome among adolescents?
- New insights into the expression of androgen and estrogen receptors of the appendix testis in congenital cryptorchidism
- General properties of autoimmune thyroid diseases and associated morbidities
- Comparison of leptin levels in neonates born to mothers with high or low gestational weight gain
- Percentile values of serum zinc concentration and prevalence of its deficiency in Iranian children and adolescents: the CASPIAN-V study
- Nine-year overview of dyslipidemia management in children with heterozygous familial hypercholesterolemia: a university hospital outpatient lipid clinic project in Northwestern Greece
- Gesell Developmental Schedules scores and the relevant factors in children with Down syndrome
- Letters to the Editor
- Society for Pediatric Radiology (SPR) Child Abuse Committee response regarding Miller, Stolfi and Ayoub’s flawed theories about child abuse and metabolic bone disease
- Reply of Miller and Ayoub to Brown et al. Letter to the Editor
- Case Reports
- Identification of two novel variants in GAA underlying infantile-onset Pompe disease in two Pakistani families
- Hereditary vitamin D-resistant rickets: a report of four cases with two novel variants in the VDR gene and successful use of intermittent intravenous calcium via a peripheral route
- Variant analysis of HPD genes from two families showing elevated tyrosine upon newborn screening by tandem mass spectrometry (MS/MS)
- Challenges in the management of an ignored cause of hyperammonemic encephalopathy: pyruvate carboxylase deficiency
- Autoimmune polyglandular syndrome type II with co-manifestation of Addison’s and Graves’ disease in a 15-year-old boy: case report and literature review
