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. 2021 Feb 26:27:100734.
doi: 10.1016/j.ymgmr.2021.100734. eCollection 2021 Jun.

Carrier frequency and predicted genetic prevalence of Pompe disease based on a general population database

Kyung Sun Park  1
Affiliations

Carrier frequency and predicted genetic prevalence of Pompe disease based on a general population database

Kyung Sun Park. Mol Genet Metab Rep. .

Abstract

Background: The genetic prevalence of Pompe disease was estimated based on the proportion of individuals who have a causative genotype in a general population database. In addition, clinical severity for causative genotypes was assessed based on currently available locus-specific databases (LSDBs), which contain information on both genotype and clinical severity.

Methods: Genetic variants in the GAA gene in the Genome Aggregation Database (gnomAD) (v2.1.1) were analyzed in combination with LSDBs of ClinVar, ClinGen Evidence Repository, Pompe disease GAA variant database, and the Pompe Registry. Carrier frequency (CF) and predicted genetic prevalence (pGP) were estimated.

Results: Of 7 populations, East Asian and African showed higher proportions of pathogenic or likely pathogenic variants (PLPVs) associated with classic infantile-onset Pompe disease. Total CF and pGP in the overall population were 1.3% (1 in 77) and 1:23,232, respectively. The highest pGP was observed in the East Asian population at 1:12,125, followed by Non-Finnish European (1:13,756), Ashkenazi Jewish (1:22,851), African/African-American (1:26,560), Latino/Admixed American (1:57,620), South Asian (1:93,087), and Finnish (1:1,056,444).

Conclusions: Pompe disease has a higher pGP (1:23,232) than earlier accepted (1:40,000). The pGP for Pompe disease was expectedly wide by population and consistent with previous reports based on newborn screening programs (approximately 1:10,000-1:30,000).

Keywords: Carrier frequency; Clinical severity; Genetic prevalence; Pompe disease; Population database; gnomAD.

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Conflict of interest statement

The author has no competing interests.

Figures

Fig. 1
Fig. 1
Genetic variants in gnomAD, ClinVar (including ClinGen), Pompe DB, or Pompe registry. (A) All genetic variants in the ClinVar, Pompe DB, or Pompe registry. The number in parentheses gives the number of genetic variants found in ClinGen. (B) Comparison of PLPVs in gnomAD and genetic variants in ClinVar, Pompe DB, or Pompe registry. The red color number in parentheses gives the number of PLPVs classified by ClinGen. All LSDBs were accessed December 15, 2020.
Fig. 2
Fig. 2
Representative 9 pathogenic or likely pathogenic variants in the overall population. Trefoil, Trefoil (P type) domain (81–130 amino acids); Gal_m.., Gal_mutarotas_2: galactose mutarotase-like (256–318 amino acids); Glyco_hydro_31, Glycosyl hydrolases family 31 (340–824 amino acids).
Fig. 3
Fig. 3
Distribution of carrier frequency and predicted genetic prevalence in each population. (A) Distribution of carrier frequency in each population. (B) Distribution of predicted genetic prevalence in each population.
See this image and copyright information in PMC

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