Mutation analysis of the PLOD1 gene: An efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA)

Abstract

The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) is an inheritable connective tissue disorder characterized by a deficiency of lysyl hydroxylase due to mutations in PLOD1. We describe a mutation analysis strategy for the PLOD1 gene using either cDNA or gDNA or a combination thereof, which allows for reliable, time-effective and efficient mutation detection in patients with EDS VIA. We report the results obtained in 9 index patients from 12 unrelated families: three patients were homozygous for three novel mutations (p.Ile454IlefsX2, p.Ala667Thr, and p.His706Arg), four patients were homozygous for the common duplication of exons 10–16, one patient was compound heterozygous for the common duplication and p.Ile454IlefsX2, and one patient was homozygous for p.Arg319X.