Background Glycogen storage disease III (GSD III) is an autosomal recessive metabolic disorder due to disease-causing mutations in amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL), the gene encoding glycogen debrancher enzyme (GDE). GSD III is usually presented with clinical findings of liver, cardiac muscle, and skeletal muscle. The purpose of this study was to report a 43-year-old Iranian patient affected by a GSD IIIa who had muscle weakness and hepatic and cardiac abnormalities. Materials and methods To find the genetic cause of this familial case of GSD, whole exome sequencing utilizing next generation sequencing on an Illumina platform was performed on DNA sample from the proband. In addition, to confirm a novel identified mutation in this patient, Sanger sequencing was carried out using both forward and reverse primers. Moreover, different bioinformatics software and database were used to predict the pathogenicity of this mutation. Results A homozygous splice-site mutation in AGL gene (NM_000642.2: c.3837-1G > A) in the patient affected by GSD type IIIa was identified. Using Sanger sequencing, this new mutation was confirmed as homozygous state in the proband. Moreover, this mutation has not been identified in all database and our database, namely BayanGene which represents data of around 500 whole exome sequencing of Iranian Individuals. Conclusions A deleterious splice site mutation in AGL gene was identified in our patient and adds to many other previous reports and extends the spectrum of GSD IIIa. Such reports help confirm the diagnosis of the disease and to perform accurate genetic counselling for their family members.
- Amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase (AGL)
- Glycogen storage disease III (GSD III)
- Novel mutation
ASJC Scopus subject areas