RGD Reference Report - Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models   new Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources

Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene.

Authors: Quintos, JB  Guo, MH  Dauber, A 
Citation: Quintos JB, etal., J Pediatr Endocrinol Metab. 2015 Jul;28(7-8):927-32. doi: 10.1515/jpem-2014-0450.
RGD ID: 11061419
Pubmed: PMID:25741789   (View Abstract at PubMed)
PMCID: PMC4501863   (View Article at PubMed Central)
DOI: DOI:10.1515/jpem-2014-0450   (Journal Full-text)

BACKGROUND: Recently, whole exome sequencing identified heterozygous defects in the aggrecan (ACAN) gene in three families with short stature and advanced bone age. OBJECTIVE: We report a novel frameshift mutation in ACAN in a family with dominantly inherited short stature, advanced bone age, and premature growth cessation. This is the first case of targeted sequencing of ACAN in this phenotype and confirms that ACAN sequencing is warranted in patients with this rare constellation of findings. RESULTS: We present a 5 1/2-year-old male with a family history of short stature in three generations. The maternal grandfather stands 144.5 cm (Ht SDS -4.7), mother 147.7 cm (Ht SDS -2.6), and index case 99.2 cm (Ht SDS -2.7). Our prepubertal patient has significant bone age advancement (bone age 8 years at chronologic age 5 1/2 years) resulting in a poor predicted adult height of 142 cm (Ht SDS -5.1). DNA sequencing identified a novel heterozygous variant in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The mutation (p.Gly1797Glyfs*52) results in premature truncation and presumed loss of protein function. CONCLUSION: Mutations in the ACAN gene should be included in the differential diagnosis of the child with idiopathic short stature or familial short stature and bone age advancement.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Dwarfism  IAGP 11061419DNA:frameshift mutation:exon:c.5391delG (human)RGD 
Dwarfism  ISOACAN (Homo sapiens)11061419; 11061419DNA:frameshift mutation:exon:c.5391delG (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acan  (aggrecan)

Genes (Mus musculus)
Acan  (aggrecan)

Genes (Homo sapiens)
ACAN  (aggrecan)


Additional Information