Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: report of two cases

Joon Yeon Won,Seon Young Park,Jong Hoon Park,Tae-Joon Cho,Ok-Hwa Kim,Hae Ryong Song,Hye Ran Lee,Mi Hyun Song,Yonghwan Kim,Dayeon Kim,Jong-Seok Lim

doi:10.1186/s12881-019-0802-2

Abstract

BackgroundX-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL.Case presentationHere, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants.ConclusionsIn the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.

Highlights

X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration
A phenotype of a patient with a deletion of 19 amino acids was not significantly distinguishable from that of another patient with a deletion of 71 amino acids [3, 4]. It still remains elusive how the phenotype of SEDT-XL patients are linked to loss of transport protein particle complex subunit 2 (TRAPPC2) functions, it was proposed that loss of TRAPPC2 might affect either the Golgi integrity [3] or the collagen secretion level [2]
When the PCR products were run on an agarose gel, both WT and two mutants revealed a band at size of 700 bp (Fig. 2e), suggesting two possible scenarios: the first is that two TRAPPC2 variants are transcribed, but not translated

Summary

Introduction

X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. Locations of TRAPPC2 variants are not necessarily related to the phenotype of affected SEDT-XL individuals. We previously reported a missense variant at the start codon (c.1A > T) [10], and detected a novel single nucleotide deletion (c.40delG) in patients presented with SEDT-XL phenotype.

Results

Conclusion