RGD Reference Report - Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips.

Authors: Hellemans, J  Coucke, PJ  Giedion, A  De Paepe, A  Kramer, P  Beemer, F  Mortier, GR 
Citation: Hellemans J, etal., Am J Hum Genet. 2003 Apr;72(4):1040-6. Epub 2003 Mar 11.
RGD ID: 1600033
Pubmed: PMID:12632327   (View Abstract at PubMed)
PMCID: PMC1180335   (View Article at PubMed Central)

Acrocapitofemoral dysplasia is a recently delineated autosomal recessive skeletal dysplasia, characterized clinically by short stature with short limbs and radiographically by cone-shaped epiphyses, mainly in hands and hips. Genomewide homozygosity mapping in two consanguineous families linked the locus to 2q35-q36 with a maximum two-point LOD score of 8.02 at marker D2S2248. Two recombination events defined the minimal critical region between markers D2S2248 and D2S2151 (3.74 cM). Using a candidate-gene approach, we identified two missense mutations in the amino-terminal signaling domain of the gene encoding Indian hedgehog (IHH). Both affected individuals of family 1 are homozygous for a 137C-->T transition (P46L), and the three patients in family 2 are homozygous for a 569T-->C transition (V190A). The two mutant amino acids are strongly conserved and predicted to be located outside the region where brachydactyly type A-1 mutations are clustered.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IHHHumanacrocapitofemoral dysplasia  IAGP DNA:point mutations:CDS:p.P46L (137C>T), p.V190A (T569T>C) (human)RGD 
IhhRatacrocapitofemoral dysplasia  ISOIHH (Homo sapiens)DNA:point mutations:CDS:p.P46L (137C>T), p.V190A (T569T>C) (human)RGD 
IhhMouseacrocapitofemoral dysplasia  ISOIHH (Homo sapiens)DNA:point mutations:CDS:p.P46L (137C>T), p.V190A (T569T>C) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ihh  (Indian hedgehog signaling molecule)

Genes (Mus musculus)
Ihh  (Indian hedgehog)

Genes (Homo sapiens)
IHH  (Indian hedgehog signaling molecule)


Additional Information