Authors: Jackson J, Turner R, Yukutake K, Baghdasaryan E, St. Denis E, Barseghyan T, Begaj S, Pietruszka M, Valles-Ayoub Y.
Complete absence or deficiency of Lysosomal acid lipase (LAL) leads to the rare infantile disorder Wolman's Disease [1]. Decreased function of GNE can lead to GNE myopathy [2]. Although both pathological phenotypes are rare, LAL deficiency only affects 1 in every 500,000 births and dysfunction of GNE affects 1 in every 1,000,000 births, there is a higher incidence in the religious groups of the Middle East; the incidence is projected to be as high as 1 in every 4,200 births [3,4]. The LIPA gene encodes for LAL while the GNE gene encodes for UDPN- acetylglucosamine (GlcNAc) 2-epimerase/N-acetylmannosamine (ManNAc) kinase [4,5]. LAL catalyzes the hydrolysis of cholesterol esters and triglycerides [6]. GlcNAc and ManNAc are responsible for the biosynthesis of sialic acid [7]. Presence of variations in GNE genes are known to impair the enzymes and lead to pathological phenotypes. This study reports the prevalence of mutations c.260G>T; p.G87V and c.894G>A; E8SJM in the lipase gene (LIPA) and c.2228T>C p.M743T in GNE gene amongst different religions. We sequenced 1,354 samples for the presence of the variations in LIPA exon 4 and 8 along with GNE exon 13(formerly exon 12). The sample population comprised individuals of varying Middle Eastern religions such as Mizrahi Jewish, Muslims, Christians, Baha’i, Catholic, Buddhist and Zoroastrian. The other religions that were not Mizrahi Jewish were classified under “Non-Jewish” to have a more even distribution. LIPA gene exon 4 variation p.G87V had a heterozygous frequency of 22 in 1,354(1.62%) with 20 of 22(90.9%) heterozygotes being Mizrahi Jewish while 2 of 22(9.09%) heterozygotes were Non-Jewish. Exon 8 splice junction mutation E8SJM, G>A transition at position 1 had a frequency of 2 in 1,354 (0.14%) with 2 of 2(100%) heterozygotes being Mizrahi Jewish. GNE exon 13 variation p.M743T (formerly exon 12 p.M712T) had a mutation frequency of 58 in 1,354(4.28%) with 5 of these 58(8.62%) samples being homozygous while 53 of the 58(91.37%) were heterozygous. In 58 samples that yielded a mutation, 54 of them were Mizarhi jewish (93.1%).
View/Download pdf