Title : Prevalence of p.G87V and p.Gln298=Variations in LIPA Gene Within Middle Eastern Population Living Around Los Angeles - Jackson_2023_Genet.Test.Mol.Biomarkers_27_319 |
Author(s) : Jackson J , Farajzadeh J , Turner R , Yukutake K , Baghdasaryan E , Denis ES , Barseghyan T , Herrera P , Begaj S , Pietruszka M , Valles-Ayoub Y |
Ref : Genet Test Mol Biomarkers , 27 :319 , 2023 |
Abstract :
Background: The LIPA gene encodes for lysosomal acid lipase (LAL), which catalyzes the hydrolysis of cholesterol esters and triglycerides. Variations in the LIPA gene impair LAL activity, predisposing patients to a rare metabolic disorder called LAL deficiency (LAL-D). The lack of functioning LAL promotes lipid accumulation and subsequent dyslipidemia, which can increase the likelihood of complications in both infants and adults. Although the worldwide prevalence is 1:500,000 births, the frequency in Mizrahi Jewish populations is projected to be as high as 1 in every 4200 births (Valles-Ayoub et al.) based on the LIPA p.G87V variant frequency among 162 individuals. Materials and Methods: This study was conducted to validate the previously reported prevalence of LAL-D in the Mizrahi Jewish population based on the pathogenic LIPA missense variants in exon 4 (c.260G>T; p.G87V) and exon 8 (c.894G>A; p.Gln298=) using a larger cohort of those with Middle Eastern ancestry living around Los Angeles. Among the 1184 individual samples sequenced, 660 self-reported as Mizrahi Jewish, while the remaining 524 came from other Middle Eastern groups labeled as "non-Jewish." Results: Of the 1184 samples, 22 alleles of the exon 4 variant were identified (1.85%), and 2 alleles of the exon 8 variant were identified (0.16%). For the exon 4 variant, 20 of 22 (90.9%) heterozygotes were Mizrahi Jewish, while 2 of 22 (9.09%) heterozygotes were "non-Jewish." For the exon 8 variant, 2 of 2 (100%) heterozygotes were Mizrahi Jewish. This suggests that the prevalence of LAL-D in this population is 1 in 900, which suggests that LAL-D may be 4.6% higher in the Mizrahi Jewish population in previous reports. Conclusion: These findings show increased prevalence of LIPA gene exon 4 variation p.G87V in the Middle East population when compared to the general population, indicating the need for prenatal screening in those of Mizrahi Jewish ancestry. |
PubMedSearch : Jackson_2023_Genet.Test.Mol.Biomarkers_27_319 |
PubMedID: 37903030 |
Gene_locus related to this paper: human-LIPA |
Mutation | Q298H_human-LIPA G87V_human-LIPA |
Gene_locus | human-LIPA |
Disease | Wolman disease WD, Cholesterol Ester Storage Disease, CESD |
Jackson J, Farajzadeh J, Turner R, Yukutake K, Baghdasaryan E, Denis ES, Barseghyan T, Herrera P, Begaj S, Pietruszka M, Valles-Ayoub Y (2023)
Prevalence of p.G87V and p.Gln298=Variations in LIPA Gene Within Middle Eastern Population Living Around Los Angeles
Genet Test Mol Biomarkers
27 :319
Jackson J, Farajzadeh J, Turner R, Yukutake K, Baghdasaryan E, Denis ES, Barseghyan T, Herrera P, Begaj S, Pietruszka M, Valles-Ayoub Y (2023)
Genet Test Mol Biomarkers
27 :319