Identification of a novel GLB1 mutation in a consanguineous Pakistani family affected by rare infantile GM1 gangliosidosis
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Monosialotetrahexosylganglioside (GM1) is a rare lysosomal storage disorder caused by the deficiency of beta-galactosidase (\(\upbeta \)-Gal) encoded by galactose beta 1 (GLB1). It is clinically characterized by developmental delay attributed to multifold accumulation of GM1 gangliosides in nerve cells. In this study, we present a case of infantile GM1 gangliosidosis in a consanguineous Pakistani family. The child was presented with developmental delay, hepatosplenomegaly and recurrent chest infections at 7.5 months of age. Radiological and biochemical investigations including magnetic resonance imaging (MRI), bone marrow biopsy and urine oligosaccharide analyses suggested lysosomal storage disorder. Significantly low levels of \(\upbeta \)-Gal enzyme confirmed the diagnosis of GM1 gangliosidosis. DNA sequencing of GLB1 identified a homozygous 2-bp deletion c.881-882delAT (p.Tyr294Terfs) in exon 8. In silico analysis supported the deleterious effect of the variant. This study extends GLB1 mutation spectrum and should benefit genetic counselling and prenatal diagnosis of the affected family.
KeywordsGM1 gangliosidosis beta-galactosidase novel mutation GLB1 gene
We thank the family members for participating in this study. The Higher Education Commission of Pakistan is acknowledged for supporting B. Z. under an Indigenous Ph.D. Fellowship scheme (PIN: 213-52789-2BM2). This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
- Hall T. A. 1999 BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp. Ser. 41, 95–98.Google Scholar
- Hinek A., Zhang S., Smith A. C. and Callahan J. W. 2000 Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase. Am. J. Hum. Genet. 67, 23–36.CrossRefGoogle Scholar
- Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J. et al. 2015 Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405–424.CrossRefGoogle Scholar
- Santamaria R., Chabas A., Coll M. J., Miranda C. S., Vilageliu L. and Grinberg D. 2006 Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum. Mutat. 27, 1060.CrossRefGoogle Scholar