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.

中文翻译：

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p.G87V 和 p.Gln298 的患病率=居住在洛杉矶周围的中东人群中 LIPA 基因的变异。

背景：LIPA 基因编码溶酶体酸性脂肪酶 (LAL)，其催化胆固醇酯和甘油三酯的水解。LIPA 基因的变异会损害 LAL 活性，使患者容易患上一种罕见的代谢性疾病，称为 LAL 缺乏症 (LAL-D)。缺乏功能性鲎试剂会促进脂质积累和随后的血脂异常，从而增加婴儿和成人出现并发症的可能性。尽管全球出生率是 1:500,000，但根据 162 名个体中的 LIPA p.G87V 变异频率，Mizrahi 犹太人口中的频率预计将高达每 4200 名新生儿中就有 1 人（Valles-Ayoub 等人）。材料和方法：本研究的目的是根据外显子 4（c.260G>T；p.G87V）和外显子 8（c.260G>T；p.G87V）和外显子 8（c.260G>T；p.G87V）中的致病性 LIPA 错义变异来验证之前报道的 Mizrahi 犹太人群体中 LAL-D 的患病率。 894G>A；p.Gln298=) 使用了居住在洛杉矶附近的更多具有中东血统的人群。在测序的 1184 个个体样本中，660 个自称是米兹拉希犹太人，而其余 524 个来自其他被标记为“非犹太人”的中东群体。结果：在1184个样本中，鉴定出22个外显子4变异等位基因（1.85%），鉴定出2个外显子8变异等位基因（0.16%）。对于外显子 4 变异，22 个杂合子中有 20 个 (90.9%) 是米兹拉希犹太人，而 22 个杂合子中有 2 个 (9.09%) 是“非犹太人”。对于外显子 8 变异，2 个杂合子中有 2 个 (100%) 是米兹拉希犹太人。这表明该人群中 LAL-D 的患病率为 900 分之一，这表明在之前的报告中米兹拉希犹太人群体中 LAL-D 的患病率可能高出 4.6%。结论：这些研究结果表明，与一般人群相比，中东人群中 LIPA 基因外显子 4 变异 p.G87V 的患病率有所增加，这表明需要对米兹拉希犹太血统的人群进行产前筛查。