Haplotype analysis and origin of the most common pathogenic mutation causing Mucolipidosis II and III alpha/beta in Brazilian patients

• Published in: Gene reports Vol. 19; p. 100645
• Main Authors: Soares, Malu Bettio, Turchetto-Zolet, Andreia C., Schwartz, Ida V.D., Sperb-Ludwig, Fernanda
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.06.2020
• Subjects: Haplotype analysis; Linkage disequilibrium; Mucolipidosis II/III alpha/beta; Mucolipidosis II/III alpha/beta; Haplotype analysis; Linkage disequilibrium
• ISSN: 2452-0144; 2452-0144
• DOI: 10.1016/j.genrep.2020.100645

Mucolipidosis II/III alpha/beta are autosomal recessive disorders caused by defective activity of N-acetylglucosamine-1-phosphotrasnferase (GlcNac-1-phosphotransferase), a hexameric enzyme complex encoded by two genes: GNPTAB and GNPTG. This enzyme has a key role in lysosomal hydrolase trafficking. Mutations in GNPTAB gene cause a spectrum of phenotypes, and c.3503_3504delTC is the most frequent mutation in patients. This study aims to characterize haplotypes of ML II/III alpha/beta patients presenting c.3503_3504delTC to understand its high frequency among patients. Fifteen patients and 100 controls were analyzed. Software analysis allowed a network construction to evaluate relations between haplotypes found: 11 in patients (7 bearing c.3503_3504delTC) and 28 in controls. One common haplotype was found, presenting a core that appeared in n = 6/7 of haplotypes bearing c.3503_3504delTC. A strong linkage disequilibrium (LD) was observed between the core markers. A founding effect is suggested because 50% of alleles presented a common origin. •Characterize haplotypes of ML II/III alpha/beta in patients presenting c.3503_3504delTC•Were found 11 different haplotypes in patients and 28 in controls•Strong linkage disequilibrium was showed between the haplotype core markers.•In patients 50% of alleles presented common origin.