Identification of a novel heterozygous mutation of the Aggrecan gene in a household with idiopathic brief stature and a number of intervertebral disc herniation.
J Hum Genet. 2017 Jul;62(7):717-721
Authors: Dateki S, Nakatomi A, Watanabe S, Shimizu H, Inoue Y, Baba H, Yoshiura KI, Moriuchi H
Aggrecan is a important proteoglycan part of the extracellular matrix of the expansion plates and articular cartilage and has a key position within the biophysical and biomechanical properties of cartilage. Not too long ago, heterozygous mutations within the ACAN gene, which encodes aggrecan, have been recognized in sufferers with brief stature and accelerated bone age. We herein report one other household with a heterozygous ACAN mutation related to idiopathic brief stature together with accelerated bone age and early-onset herniation of the lumbar discs on the ranges of L1/2 by L5/S1. Entire-exome sequencing recognized a novel heterozygous frameshift mutation within the ACAN gene (c.1744delT; p.Phe582fs*69) in all the affected relations however not within the unaffected one, offering additional proof that ACAN haploinsufficiency causes brief stature with superior bone maturation. As well as, we advocate early-onset a number of disc herniation as a novel phenotype related to ACAN haploinsufficiency.
PMID: 28331218 [PubMed – indexed for MEDLINE]