Dataset Information
Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations.
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ABSTRACT: 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.
SUBMITTER: Gkourogianni A
PROVIDER: S-EPMC5413162 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Publications
Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan Mutations.
The Journal of clinical endocrinology and metabolism 20170201 2
<h4>Context</h4>Heterozygous mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with accelerated skeletal maturation.<h4>Objective</h4>We sought to characterize the phenotypic spectrum and response to growth-promoting therapies.<h4>Patients and methods</h4>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-gen ...[more]