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Clin Chim Acta. 2017 Jun;469:126-129. doi: 10.1016/j.cca.2017.04.004. Epub 2017 Apr 7.

Novel pathogenic ACAN variants in non-syndromic short stature patients.

Author information

1
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
2
Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China.
3
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
4
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; Genetic and Metabolic Central Laboratory, Guangxi Maternal and Child Health Hospital, Nanning, Guangxi, PR China; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, United States; Department of Neurology, Harvard Medical School, Boston, MA, United States. Electronic address: yiping.shen@childrens.harvard.edu.

Abstract

BACKGROUND:

Pathogenic variants of ACAN have been reported to cause spondyloepiphyseal dysplasia Kimberley type, spondyloepimetaphyseal dysplasia, familial osteochondritis dissecans and idiopathic short stature with normal to advanced bone age. A recent international cohort study significantly expanded the ACAN mutation spectrum, further delineated the heterogeneous clinical characteristics of ACAN mutation patients. The prevalence of ACAN mutation in short stature patients is yet unknown.

METHODS:

Here we set to assess the frequency of ACAN variants among a cohort of 218 Chinese children with non-syndromic short stature.

RESULTS:

We identified three novel truncating variants at the 5' end of ACAN gene. All these pathogenic variants co-segregate with severe short stature phenotype in families. In addition, none of the probands showed significant advanced bone age. All affected individuals showed no signs of significant dysmorphic features or skeletal abnormities. The prevalence of ACAN defect in this cohort is estimated to be 1.4% (3/218). It is higher among families with parents also affected with severe short stature, up to 7.0% (3/43) if parental height is <2.5 SD or 16.7% (3/18) if parental height is <3.0 SD.

CONCLUSION:

Our data suggest that ACAN mutation is a relative common cause of familial severe short stature.

KEYWORDS:

ACAN mutation; Bone age; Pathogenic variants; Prevalence; Short stature

PMID:
28396070
DOI:
10.1016/j.cca.2017.04.004
[Indexed for MEDLINE]

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