Whole-exome sequencing in a Japanese pedigree implicates a rare non-synonymous single-nucleotide variant in BEST3 as a candidate for mandibular prognathism

• Published in: Bone (New York, N.Y.) Vol. 122; pp. 193 - 198
• Main Authors: Kajii, Takashi S., Oka, Akira, Saito, Fumio, Mitsui, Jun, Iida, Junichiro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2019
• Subjects: Bestrophin 3; Endochondral growth; Genetics; Japanese; Mandibular prognathism; Whole-exome sequencing; GWAS; SNP; ANB; PDGF; Whole-exome sequencing; Genetics; Mandibular prognathism; SNV; Bestrophin 3; Endochondral growth; Japanese; EGFR
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2019.03.004

Mandibular prognathism is a phenotype of facial deformity seen in populations around the world, but with higher incidence among East Asian populations. Five genome-wide nonparametric linkage analyses and a genome-wide association study to identify susceptibility loci of the phenotype have shown inconsistent results. To explore variants related to mandibular prognathism, we undertook whole-exome sequencing in a Japanese pedigree. The pedigree was ascertained as mandibular prognathism. The pedigree comprised 15 individuals from 4 generations. Four affected individuals across 2 generations and 5 unaffected individuals were chosen for whole-exome sequencing. Five non-synonymous single-nucleotide variants (SNVs) of UBASH3B, OR6M1, OR8D4, OR8B4, and BEST3 genes were detected in all 4 affected individuals, but in none of the 5 unaffected individuals. A non-synonymous SNV of the BEST3 gene, Chr12(GRCh37):g.70048878G>T, NM_032735.2:c.1816C>A, p.(L606I), was identified as rare missense variant. BEST3 is located on chromosome 12q15 and encodes bestrophin 3 from the bestrophin family of anion channels. The 4 other non-synonymous SNVs of UBASH3B, OR6M1, OR8D4, and OR8B4 were not considered plausible candidates for mandibular prognathism. Our whole-exome sequencing implicates a rare non-synonymous SNV of BEST3 as a candidate for mandibular prognathism in the Japanese pedigree.
•Whole-exome sequencing in a Japanese pedigree with mandibular prognathism was done.•Five non-synonymous single-nucleotide variants (SNVs) were identified.•A non-synonymous SNV (p.L606I) of BEST3 gene was a novel missense variant.•The sequencing implicates the variant as a candidate for mandibular prognathism.