Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373862" target="_blank" >RIV/00216208:11130/17:10373862 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/17:10373862

Result on the web

<a href="https://doi.org/10.1210/jc.2016-3313" target="_blank" >https://doi.org/10.1210/jc.2016-3313</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1210/jc.2016-3313" target="_blank" >10.1210/jc.2016-3313</a>

Result language

angličtina

Original language name

Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations

Original language description

Context: Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation. Objective: We sought to characterize the phenotypic spectrum and response to growth-promoting therapies. Patients and Methods: One hundred three individuals (57 females, 46 males) from 20 families with autosomal dominant short stature and heterozygous ACAN mutations were identified and confirmed using whole-exome sequencing, targeted next-generation sequencing, and/or Sanger sequencing. Clinical information was collected from the medical records. Results: Identified ACAN variants showed perfect cosegregation with phenotype. Adult individuals had mildly disproportionate short stature [median height, -2.8 standard deviation score (SDS); range, -5.9 to -0.9] and a history of early growth cessation. The condition was frequently associated with early-onset osteoarthritis (12 families) and intervertebral disc disease (9 families). No apparent genotype-phenotype correlation was found between the type of ACAN mutation and the presence of joint complaints. Childhood height was less affected (median height, -2.0 SDS; range, -4.2 to -0.6). Most children with ACAN mutations had advanced bone age (bone age - chronologic age; median, + 1.3 years; range, + 0.0 to + 3.7 years). Nineteen individuals had received growth hormone therapy with some evidence of increased growth velocity. Conclusions: Heterozygous ACAN mutations result in a phenotypic spectrum ranging from mild and proportionate short stature to a mild skeletal dysplasia with disproportionate short stature and brachydactyly. Many affected individuals developed early-onset osteoarthritis and degenerative disc disease, suggesting dysfunction of the articular cartilage and intervertebral disc cartilage. Additional studies are needed to determine the optimal treatment strategy for these patients.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30202 - Endocrinology and metabolism (including diabetes, hormones)

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

The Journal of Clinical Endocrinology &amp; Metabolism

ISSN

0021-972X

e-ISSN

—

Volume of the periodical

102

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

460-469

UT code for WoS article

000397240900018

EID of the result in the Scopus database

2-s2.0-85012081706