Document Type : case report

Authors

1 Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Iran

2 Innovative Medical Research Center, Islamic Azad University, Mashhad, Iran.

3 General Paediatrics, Evelina London Children’s Hospital, Guy’s and St. Thomas’ National Health Service Foundation Trust, London, United Kingdom

4 Department of Pediatric Endocrinology and Metabolism, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Medical Genetics, Next Generation Genetic Polyclinic, Mashhad, Iran

6 Molecular and Clinical Sciences Institute, St. George’s, University of London, London, United Kingdom

Abstract

Aim: Short stature is estimated to account for half of the new visits to pediatric endocrine practices, therefore evaluating the underlying cause seems essential in order to choose the best treatment. Recently, some studies revealed the impact of ACAN, which encodes for aggrecan, mutations on growth ranging from mild idiopathic short stature to severe skeletal dysplasia.

Methods: Here, we describe clinical and molecular characteristics of an Iranian family with short stature using exome sequencing and co-segregation analysis through Sanger sequencing.

Results: A novel variant of ACAN mutation c.1604delG (p.Arg535fs) was identified in heterozygote pattern which was confirmed through co-segregation analysis in family members.

Conclusion: We have found a novel variant within the ACAN gene in association with insignificant bone abnormality without a high incidence of familiar bone malformation. In order to achieve better clinical outcomes, we suggest genetic testing at an earlier age and also long-term GH treatment for children who are at risk of ACAN mutations. Children who are born small for gestational age, or who have persistent short stature, advanced bone age, midfacial hypoplasia, joint problems, or broad toes, can be candidates for ACAN sequencing.

Keywords