Identification of a Locus for Autosomal-Dominant PPCD on 8q22.3–q24.12 and a Unique Variant in Intron 1 of GRHL2
(A) Abridged pedigree structure of PPCD-affected family C15 of Czech origin. L indicates samples used for SNP genotyping and linkage analysis. WES and WGS indicate DNA samples analyzed by whole-exome and whole-genome sequencing, respectively. Individuals who were heterozygous for the GRHL2 c.20+544G>T mutation are indicated by +/−, and those lacking the mutation are indicated by −/−.
(B) Linkage analysis identified a single locus with a significant LOD score (>3, red line) spanning chromosome 8q22.3–q24.12 from chr8.hg38:100,821,039–119,725,923 with a maximum LOD score of 4.38 (green line).
(C) Heterozygous variant c.20+544G>T (chr8.hg38:101,493,333G>T) identified by WGS, located in intron 1 of GRHL2 (GenBank: NM_024915; Ensembl: ENST00000251808.7), was confirmed by Sanger sequencing.
(D) Boxed region on chr8 depicts the PPCD4 linked interval, and the position and exon structure of the GRHL2 gene (5′ to 3′) and intronic mutation are shown.