Diagnostic tests require Specialist referral only.
Familial testing through Genetic Services only.
Genetic Health Service NZ can be contacted on 0800 476 123.
Specimen Collection 4 mL Paediatric EDTA Blood (Preferred) 8 mL Adult EDTA Blood
For paediatric samples a minimum of 0.5ml blood EDTA can be processed. (Microcollect)
Transport all bloods at room temperature within 24-48 hours. If necessary specimens can be refrigerated overnight for transport at room temperature the following day.
For testing of other sample types please contact the laboratory prior to sending.
Turnaround Time: 13 weeks Contact Information
Contact Molecular Genetics via:
Lablink ext 22000
Mark Greenslade (Technical Head) ext 22010
Pippa Grainger (Section leader) ext 22014
Two mutations in the FGFR3 gene cause more than 99 percent of cases of achondroplasia. Both mutations lead to the same change in building blocks (amino acids) that make up the fibroblast growth factor receptor 3 protein. Specifically, the amino acid glycine is replaced with the amino acid arginine at protein position 380 (Gly380Arg or G380R). Researchers believe that this genetic change causes the receptor to be overly active, which leads to the disturbances in bone growth seen with this disorder.
A single FGFR3 mutation has been identified in people with Crouzonodermoskeletal syndrome. This genetic change replaces the amino acid alanine with the amino acid glutamic acid at position 391 of the fibroblast growth factor receptor 3 protein (Ala391Glu or A391E). it has not been determined how this mutation leads to the signs and symptoms of this disorder, but the altered receptor appears to disrupt the normal growth of skull bones and affect skin pigmentation.
Several mutations in the FGFR3 gene have been identified in people with hypochondroplasia. Many cases are caused by one of two specific FGFR3 mutations, both of which lead to the same change in amino acids in the fibroblast growth factor receptor 3 protein. Specifically, the amino acid asparagine is replaced with the amino acid lysine at protein position 540 (Asn540Lys or N540K). Other FGFR3 mutations probably cause a small number of cases of hypochondroplasia. Although the effects of these mutations have not been explained, they probably cause the receptor to be mildly overactivated, which leads to the disturbances in bone growth seen with this disorder.
A single mutation in the FGFR3 gene has been shown to cause Muenke syndrome. This change substitutes the amino acid arginine for the amino acid proline at position 250 in the fibroblast growth factor receptor 3 protein (Pro250Arg or P250R). This mutation results in the production of a receptor that is overly active, which allows the bones of the skull to fuse before they should.
The Pro250Arg mutation has also been identified in some people with apparently isolated coronal craniosynostosis. This condition is characterized by a premature fusion of the growth line that runs across the top of the head from ear to ear (the coronal suture). People with isolated coronal craniosynostosis do not have the other features of Muenke syndrome, such as hearing loss, hand and foot abnormalities, or developmental delay.
At least 10 mutations in the FGFR3 gene have been identified in people with thanatophoric dysplasia type I. Most of these mutations change a single amino acid in the fibroblast growth factor receptor 3 protein. The most common mutation substitutes the amino acid cysteine for the amino acid arginine at protein position 248 (Arg248Cys or R248C). Other mutations cause the protein to be longer than normal.
Only one mutation has been shown to cause thanatophoric dysplasia type II. This mutation replaces the amino acid lysine with the amino acid glutamic acid at position 650 of the fibroblast growth factor receptor 3 protein (Lys650Glu or K650E). This change affects a different part of the
protein than the mutations that cause thanatophoric dysplasia type I.
The genetic changes responsible for both types of thanatophoric dysplasia cause the
receptor to be overactivated, which leads to the severe problems with bone growth seen in these conditions. It is not known how
mutations lead to the brain and skin abnormalities associated with thanatophoric dysplasia.
Molecular genetic testing for
For more information about the Molecular Genetics service:
Molecular Genetics information page