Identification of a novel heterozygous mutation of the Aggrecan gene in a family with idiopathic short stature and multiple intervertebral disc herniation

Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates and articular cartilage and has a key role in the biophysical and biomechanical properties of cartilage. Recently, heterozygous mutations in the ACAN gene, which encodes aggrecan, have been identified in p...

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Bibliographic Details
Published in:Journal of human genetics 2017-07, Vol.62 (7), p.717-721
Main Authors: Dateki, Sumito, Nakatomi, Akiko, Watanabe, Satoshi, Shimizu, Hitomi, Inoue, Yukiko, Baba, Hideo, Yoshiura, Koh-Ichiro, Moriuchi, Hiroyuki
Format: Article
Language:English
Subjects:
Age
Aggrecan
Aggrecans - genetics
Back
Base Sequence
Body Height - genetics
Cartilage
Cartilage (articular)
Extracellular matrix
Family
Frameshift mutation
Growth plate
Haploinsufficiency
Haploinsufficiency - genetics
Heterozygote
Humans
Intervertebral Disc Degeneration - genetics
Intervertebral Disc Displacement - genetics
Intervertebral discs
Male
Mechanical properties
Mutation
Mutation - genetics
Phenotype
Phenotypes
Proteoglycans
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Summary:Aggrecan is a critical proteoglycan component of the extracellular matrix of the growth plates and articular cartilage and has a key role in the biophysical and biomechanical properties of cartilage. Recently, heterozygous mutations in the ACAN gene, which encodes aggrecan, have been identified in patients with short stature and accelerated bone age. We herein report another family with a heterozygous ACAN mutation associated with idiopathic short stature along with accelerated bone age and early-onset herniation of the lumbar discs at the levels of L1/2 through L5/S1. Whole-exome sequencing identified a novel heterozygous frameshift mutation in the ACAN gene (c.1744delT; p.Phe582fs*69) in all of the affected family members but not in the unaffected one, providing further evidence that ACAN haploinsufficiency causes short stature with advanced bone maturation. In addition, we advocate early-onset multiple disc herniation as a novel phenotype associated with ACAN haploinsufficiency.
ISSN:1434-5161
1435-232X
DOI:10.1038/jhg.2017.33