Founder Effect of the c. <scp>500G</scp> &gt;A Variant in South Asian Patients With Inherited <scp>GPD1</scp> Deficiency: Report on 16 Patients and Variant Review

Only a few studies describe five (or more) patients with inherited glycerol-3-phosphate dehydrogenase 1 (GPD1) deficiency, often termed transient infantile hypertriglyceridemia (HTGTI). We report 18 additional patients with HTGTI (confirmed molecular diagnosis in 16, a variant of uncertain significance in two), most of whom presented in infancy with hepatomegaly. A significant negative correlation was noted between age at presentation and serum triglyceride levels. Except for two, all our patients have homozygous GPD1 variants, wherein the c.500G>A (p.Gly167Asp) variant was the most common (10 patients). Other variants identified included c.220-1G>T, c.398C>T (p.Ser133Leu, unpublished), c.806G>A (p.Arg269Gln), and c.685C>T (p.Arg229Trp, novel). Homozygosity matching in patients with the biallelic c.500G>A variant showed that the GPD1 gene is located within the only shared region of homozygosity (> 1 Mb). These patients also have a similar homozygous haplotype around the variant, construing its founder effect in South Asian patients with inherited GPD1 deficiency. Targeted testing for c.500G>A could be considered as a first-tier evaluation strategy in South Asian patients with HTGTI. However, given our limited sample size, further validatory studies are needed.