How to Cite this Article: Dwyer E, Hyland J, Modaff P, Pauli RM. 2010. Genotype–phenotype correlation in DTDST dysplasias: Atelosteogenesis type II and diastrophic dysplasia variant in one family. Am J Med Genet Part A 152A:3043–3050.
Genotype–phenotype correlation in DTDST dysplasias: Atelosteogenesis type II and diastrophic dysplasia variant in one family†
Version of Record online: 12 NOV 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 12, pages 3043–3050, December 2010
How to Cite
Dwyer, E., Hyland, J., Modaff, P. and Pauli, R. M. (2010), Genotype–phenotype correlation in DTDST dysplasias: Atelosteogenesis type II and diastrophic dysplasia variant in one family. Am. J. Med. Genet., 152A: 3043–3050. doi: 10.1002/ajmg.a.33736
- Issue online: 23 NOV 2010
- Version of Record online: 12 NOV 2010
- Manuscript Accepted: 27 AUG 2010
- Manuscript Received: 29 JUL 2010
- family of bone dysplasias;
- diastrophic dysplasia;
- atelosteogenesis type II;
- genotype–phenotype correlation;
- diastrophic dysplasia sulfate transporter
Mutations in diastrophic dysplasia sulfate transporter (DTDST) cause a spectrum of autosomal recessive chondrodysplasias. In decreasing order of severity, they include processes designated as achondrogenesis type IB (ACG-1B), atelosteogenesis type II (AO2), diastrophic dysplasia (DTD), diastrophic dysplasia variant (DTDv), and recessively inherited multiple epiphyseal dysplasia (rMED). This is the first report of an extended family with unequivocally distinct phenotypes on the DTDST spectrum. Two siblings have DTDv and their first cousin had AO2. They all share the common Finnish mutation (IVS1 + 2C>T). The two patients with DTDv have the previously reported R279W extracellular domain missense mutation. The second mutation in the patient with AO2 is c.172delA, a deletion of one nucleotide causing a previously unreported frameshift mutation. This is the first published case of an individual with a frameshift mutation combined with the Finnish mutation. These three patients provide an opportunity, in concert with a review of previous literature, to further examine the genotype–phenotype correlation of DTDST. Analysis suggests that, while the DTDST family of disorders contains at least seven different conditions, mutations in the DTDST gene, in fact, appear to cause a phenotypic continuum. Furthermore, DTDST genotype alone is an imperfect predictor of clinical severity along this continuum. © 2010 Wiley-Liss, Inc.