Congenital Joint Dislocations Caused by Carbohydrate Sulfotransferase 3 Deficiency in Recessive Larsen Syndrome and Humero-Spinal Dysostosis

Pia Hermanns, Sheila Unger, Antonio Rossi, Antonio Perez-Aytes, Hector Cortina, Luisa Bonafé, Loredana Boccone, Valeria Setzu, Michel Dutoit, Luca Sangiorgi, Fabio Pecora, Kerstin Reicherter, Gen Nishimura, Jürgen Spranger, Bernhard Zabel, Andrea Superti-Furga

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1368-1374
Number of pages7
JournalAmerican Journal of Human Genetics
Volume82
Issue number6
DOIs
Publication statusPublished - Jun 6 2008

ASJC Scopus subject areas

  • Genetics

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    Hermanns, P., Unger, S., Rossi, A., Perez-Aytes, A., Cortina, H., Bonafé, L., Boccone, L., Setzu, V., Dutoit, M., Sangiorgi, L., Pecora, F., Reicherter, K., Nishimura, G., Spranger, J., Zabel, B., & Superti-Furga, A. (2008). Congenital Joint Dislocations Caused by Carbohydrate Sulfotransferase 3 Deficiency in Recessive Larsen Syndrome and Humero-Spinal Dysostosis. American Journal of Human Genetics, 82(6), 1368-1374. https://doi.org/10.1016/j.ajhg.2008.05.006