J Genet Med.  2018 Dec;15(2):102-106. 10.5734/JGM.2018.15.2.102.

Identification of a novel heterozygous mutation of ACAN in a Korean family with proportionate short stature

• Kim YM
• Cheon CK
• Lim HH
• Yoo HW

• KMID: 2435950
• DOI: http://doi.org/10.5734/JGM.2018.15.2.102

Abstract

Aggrecan is a proteoglycan in the extracellular matrix of growth plate and cartilaginous tissues. Aggrecanopathy has been reported as a genetic cause not only for severe skeletal dysplasia but also for autosomal dominant short stature with normal to advanced bone age. We report a novel heterozygous mutation of ACAN in a Korean family with proportionate short stature identified through targeted exome sequencing. We present a girl of 4 years and 9 months with a family history of short stature over three generations. The paternal grandmother is 143 cm tall (−3.8 as a Korean standard deviation score [SDS]), the father 155 cm (−3.4 SDS), and the index case 96.2 cm (−2.9 SDS). Evaluation for short stature showed normal growth hormone (GH) peaks in the GH provocation test and a mild delayed bone age for chronological age. This subject had clinical characteristics including a triangular face, flat nasal bridge, prognathia, blue sclerae, and brittle teeth. The targeted exome sequencing was applied to detect autosomal dominant growth palate disorder. The novel variant c.910G>A (p.Asp304Asn) in ACAN was identified and this variant was found in the subject's father using Sanger sequencing. This is the first case of Korean familial short stature due to ACAN mutation. ACAN should be considered for proportionate idiopathic short stature, especially in cases of familial short stature.

Keyword

Short stature; Aggrecans; ACAN

MeSH Terms

Aggrecans
Exome
Extracellular Matrix
Family Characteristics
Fathers
Female
Grandparents
Growth Hormone
Growth Plate
Humans
Palate
Proteoglycans
Sclera
Tooth
Aggrecans
Growth Hormone
Proteoglycans