Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis


Autoria(s): Hermanns P.; Unger S.; Rossi A.; Perez-Aytes A.; Cortina H.; Bonafe L.; Boccone L.; Setzu V.; Dutoit M.; Sangiorgi L.; Pecora F.; Reicherter K.; Nishimura G.; Spranger J.; Zabel B.; Superti-Furga A.
Data(s)

2008

Resumo

Deficiency of carbohydrate sulfotransferase 3 (CHST3; also known as chondroitin-6-sulfotransferase) has been reported in a single kindred so far and in association with a phenotype of severe chondrodysplasia with progressive spinal involvement. We report eight CHST3 mutations in six unrelated individuals who presented at birth with congenital joint dislocations. These patients had been given a diagnosis of either Larsen syndrome (three individuals) or humero-spinal dysostosis (three individuals), and their clinical features included congenital dislocation of the knees, elbow joint dysplasia with subluxation and limited extension, hip dysplasia or dislocation, clubfoot, short stature, and kyphoscoliosis developing in late childhood. Analysis of chondroitin sulfate proteoglycans in dermal fibroblasts showed markedly decreased 6-O-sulfation but enhanced 4-O-sulfation, confirming functional impairment of CHST3 and distinguishing them from diastrophic dysplasia sulphate transporter (DTDST)-deficient cells. These observations provide a molecular basis for recessive Larsen syndrome and indicate that recessive Larsen syndrome, humero-spinal dysostosis, and spondyloepiphyseal dysplasia Omani type form a phenotypic spectrum.

Identificador

http://serval.unil.ch/?id=serval:BIB_D4498EE45DC0

isbn:1537-6605

pmid:18513679

doi:10.1016/j.ajhg.2008.05.006

isiid:000256647000015

Idioma(s)

en

Fonte

American Journal of Human Genetics, vol. 82, no. 6, pp. 1368-1374

Tipo

info:eu-repo/semantics/article

article