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Sci Rep. 2017 Sep 22;7(1):12225. doi: 10.1038/s41598-017-12465-6.

Genetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature.

Author information

1
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
2
Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
3
Institute of Human Genetics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
4
Institute of Human Genetics, University of Leipzig, Leipzig, Germany.
5
Institute of Human Genetics, University of Duisburg-Essen, Essen, Germany.
6
Institute of Human-Genetics, Medical Faculty, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.
7
Division of Pediatric Endocrinology, Department of Pediatrics and Neonatology, Saarland University Hospital, Homburg/Saar, Germany.
8
Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.
9
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. Christian.Thiel@uk-erlangen.de.

Abstract

Short stature is a common pediatric disorder affecting 3% of the population. However, the clinical variability and genetic heterogeneity prevents the identification of the underlying cause in about 80% of the patients. Recently, heterozygous mutations in the ACAN gene coding for the proteoglycan aggrecan, a main component of the cartilage matrix, were associated with idiopathic short stature. To ascertain the prevalence of ACAN mutations and broaden the phenotypic spectrum in patients with idiopathic short stature we performed sequence analyses in 428 families. We identified heterozygous nonsense mutations in four and potentially disease-causing missense variants in two families (1.4%). These patients presented with a mean of -3.2 SDS and some suggestive clinical characteristics. The results suggest heterozygous mutations in ACAN as a common cause of isolated as well as inherited idiopathic short stature.

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