Dataset Information

A Case of Short Stature Caused by a Mutation in the ACAN Gene.

ABSTRACT:

Introduction

Aggrecanopathies are rare disorders associated with idiopathic short stature. They are caused by pathogenic changes in the ACAN gene located on chromosome 15q26. In this study, we present a case of short stature caused by mutations in the ACAN gene.

Case presentation

A 3-year-3-month-old male patient was referred to us because of his short stature. Physical examination revealed proportional short stature, frontal bossing, macrocephaly, midface hypoplasia, ptosis in the right eye, and wide toes. When the patient was 6 years and 3 months old, his bone age was compatible with 7 years of age. The patient underwent clinical exome sequencing and a heterozygous nonsense c.1243G>T, p.(Glu415*) pathogenic variant was detected in the ACAN gene. The same variant was found in his phenotypically similar father. Our patient is the second case with ptosis.

Discussion

ACAN gene mutation should be considered in the differential diagnosis of patients with idiopathic short stature. The development and widespread use of next-generation sequencing technology has increased the diagnostic and treatment possibilities.

SUBMITTER: Karatas E

PROVIDER: S-EPMC10091005 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

A Case of Short Stature Caused by a Mutation in the <i>ACAN</i> Gene.

Karatas Emine E Demir Mikail M Ozcelik Firat F Kara Leyla L Akyurek Esra E Berber Ugur U Hatipoglu Nihal N Ozkul Yusuf Y Dundar Munis M

Molecular syndromology 20221021 2

<h4>Introduction</h4>Aggrecanopathies are rare disorders associated with idiopathic short stature. They are caused by pathogenic changes in the <i>ACAN</i> gene located on chromosome 15q26. In this study, we present a case of short stature caused by mutations in the <i>ACAN</i> gene.<h4>Case presentation</h4>A 3-year-3-month-old male patient was referred to us because of his short stature. Physical examination revealed proportional short stature, frontal bossing, macrocephaly, midface hypoplasia ...[more]

PMID: 37064332

Similar Datasets

Project description:ObjectiveACAN gene variants are an important cause of familial short stature (FSS). Appropriate growth-promoting therapies effectively improve the patient height. Here, we report a therapeutic assessment of cases of seven families of FSS patients with heterozygous ACAN variants. Our findings provide a valuable theoretical basis for the clinical diagnosis and treatment of this disease.MethodsFrom December 2020 to June 2021, 32 FSS patients were examined in Tianjin Medical University General Hospital (Tianjin, China) by whole-exome sequencing to determine whether ACAN variants were present. Their clinical data were summarized and scrupulously analyzed.ResultsWe found seven novel heterozygous ACAN variants: c.1051 + 2T > A, c.313T > C (p.S105P), c.2660C > G (p.S887X), c.2153C > A (p. T718K), c.7243delG (p.D2415Tfs*4), c.2911G > T (p.G971X), c.758-7T > C. All seven patients had proportionate short stature and mild skeletal dysplasia. Endocrine examination results were normal. Only one of the patients had an advanced bone age (1.1 years older than chronological age), whereas the other patients had normal bone ages. All of them had a family history of short stature, with or without osteoarthritis or intervertebral disc disease. All seven patients accepted treatment with recombinant human growth hormone (rhGH) and were regularly followed up. One patient did not come at the follow-up visit. The height of the remaining six patients before and after the treatment was -2.89 ± 0.68 SDS, -1.91 ± 0.93 SDS, respectively, with a treatment course of 1.85 ± 1.91 years. A good therapeutic response was observed in all of them.ConclusionsIn this study, seven novel heterozygous variants in ACAN were discovered, which expanded the spectrum of the already established ACAN pathogenic variants. In FSS cohort, the proportion of ACAN variants accounted was large. The treatment with rhGH effectively increased the patient height, but further studies with longer follow-up periods and more extensive observations are required to elucidate the long-term effect.