A novel mutation in the ACAN gene in a family with autosomal dominant short stature and intervertebral disc disease

Abstract

Heterozygous mutations in the ACAN gene have been reported in individuals with short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans. We report a family with a phenotypic constellation carrying a novel mutation in the ACAN gene. The proband was a 7-year-old Japanese girl with short stature. Her mother and maternal grandmother also had short stature and intervertebral disc disease. We analyzed the ACAN gene in the family and identified a novel heterozygous mutation: c.4634delT, Leu1545Profs*11.

Fig. 1. Clinical information of the family members.

A Growth chart of the proband. Heights and weights are shown as black points. B X-ray of the proband’s left hand. Mild shortening of the 4th and 5th metacarpals and shortening of the 1st distal phalanx are shown. The bone age was interpreted as 8 years and 10 months using the Greulich and Pyle method. C X-ray of the proband’s feet. Cone-shaped epiphyses of the left 1st and 4th metatarsals and large epiphyses of the 5th distal phalanges are shown. D, E Lumbar spine X-rays of the proband’s mother and maternal grandmother. Narrowed intervertebral spaces and endplate irregularities are shown. F Pedigree of the studied family. The arrow indicates the proband (III-3). The family members with short stature carrying ACAN mutations are indicated with filled symbols. Ages and heights in standard division score are reported below each symbol.

Fig. 2. Exon 12 of the ACAN gene.

A The black area on the exon 12 denotes various numbers tandem repeat. Variant c.4634delT (black triangle) is reported in this study. B Partial sequence (reverse complemented). The upper panel shows a chromatogram of the proband that had a heterozygous mutation, c.4634delT, Leu1545Profs*11, which is denoted by an arrow. The lower panel shows a chromatogram of the wild-type sequence.