Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature.

Based on the observation of reduced stature in relatives of patients with acromesomelic dysplasia, Maroteaux type (AMDM), caused by homozygous or compound heterozygous mutations in natriuretic peptide receptor-B gene (NPR2), it has been suggested that heterozygous mutations in this gene could be responsible for the growth impairment observed in some cases of idiopathic short stature (ISS). We enrolled 192 unrelated patients with short stature and 192 controls of normal height and identified seven heterozygous NPR2 missense or splice site mutations all in the short stature patients, including one de novo splice site variant. Three of the six inherited variants segregated with short stature in the family.

Whole exome sequencing to identify genetic causes of short stature.

Background/aims: Short stature is a common reason for presentation to pediatric endocrinology clinics. However, for most patients, no cause for the short stature can be identified. As genetics plays a strong role in height, we sought to identify known and novel genetic causes of short stature.

Large-scale pooled next-generation sequencing of 1077 genes to identify genetic causes of short stature.

Context: The majority of patients presenting with short stature do not receive a definitive diagnosis. Advances in genetic sequencing allow for large-scale screening of candidate genes, potentially leading to genetic diagnoses.

Objectives: The purpose of this study was to discover genetic variants that contribute to short stature in a cohort of children with no known genetic etiology.