Analysis of the inheritance pattern of a Chinese family with phaeochromocytomas through whole exome sequencing

Abstract

Phaeochromocytomas (PCCs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors. Most familial PCC/PGLs have been detected to be autosomal dominantly inherited. However, this study was undertaken in a family with PCCs to determine candidate genes in a dominant or recessive inheritance pattern. After excluding mutations in ten PCC/PGL susceptibility genes by Sanger sequencing, we used whole exome sequencing for screening on the four family members to discover novel candidate genes associated with PCCs. Based on the inexistence of non-synonymous mutations or indels in the ten known genes and the structure of this pedigree, 3 damaging loci with dominant inheritance pattern, and 5 damaging loci with recessive homozygous inheritance pattern and 6 damaging genes with compound heterozygous inheritance pattern were narrowed down to indicate the association with PCCs. According to the Gene Ontology (GO) category analysis on the combined results, cell adhesion showed the most significant enrichment.

Keywords: CT; CTA; Computed Tomography; Computed Tomography Angiography; FDR; False Discovery Rate; GO; Gene Ontology; Indel; Inheritance pattern; Insertion–Deletion; LOD; Logarithm of Odds; MEN2; MN; Metanephrine; Multiple Endocrine Neoplasia Type 2; NF1; NMN; NPL; NS; Neurofibromatosis Type 1; Non-synonymous; Nonparametric Linkage; Normetanephrine; PCCs; PGLs; Paragangliomas; Phaeochromocytomas; SNP; SNV; SS; Sanger sequencing; Single Nucleotide Polymorphism; Single Nucleotide Variation; Splice Site; TR; Target Region; VHL; Von Hippel–Lindau; Whole exome sequencing.