title: Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G>A) in various racial and ethnic groups.
abstract: Cholesteryl ester storage disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only ∼3%-5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations. To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study. The combined c.894G>A allele frequencies from the two cohorts ranged from 0.0005 (Asian) to 0.0017 (Caucasian and Hispanic), which translated to carrier frequencies of 1 in 1,000 to ∼1 in 300, respectively. No African-American heterozygotes were detected. Additionally, by surveying the available literature, c.894G>A was estimated to account for 60% (95% confidence interval [CI]: 51%-69%) of reported mutations among multiethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is ∼0.8 per 100,000 (∼1 in 130,000; 95% CI: ∼1 in 90,000 to 1 in 170,000).
  
  
  CONCLUSIONS
  These data indicate that CESD may be underdiagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies, since c.894G>A is not common in these racial groups.
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors: Stuart A
authors: SA
authors: Scott
authors: Benny
authors: B
authors: Liu
authors: Irina
authors: I
authors: Nazarenko
authors: Suparna
authors: S
authors: Martis
authors: Julia
authors: J
authors: Kozlitina
authors: Yao
authors: Y
authors: Yang
authors: Charina
authors: C
authors: Ramirez
authors: Yumi
authors: Y
authors: Kasai
authors: Tommy
authors: T
authors: Hyatt
authors: Inga
authors: I
authors: Peter
authors: Robert J
authors: RJ
authors: Desnick
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000208:ethnology / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001213:Asian / Q000208:ethnology / Q000235:genetics; D015217:Cholesterol Ester Storage Disease / Q000208:ethnology* / Q000235:genetics*; D005006:Ethnicity / Q000208:ethnology* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D006579:Heterozygote; D006630:Hispanic or Latino / Q000208:ethnology / Q000235:genetics; D006801:Humans; D007585:Jews / Q000208:ethnology / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009518:New York; D015995:Prevalence; D012189:Retrospective Studies; D002787:Sterol Esterase / Q000235:genetics*; D044465:White People / Q000208:ethnology / Q000235:genetics; D055815:Young Adult
chemical_list: C503451:LIPA protein, human; D002787:Sterol Esterase