Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis.
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.
Hermanns
Pia
P
Center for Pediatrics and Adolescent Medicine, University of Freiburg, 79106 Freiburg, Germany.
Unger
Sheila
S
Rossi
Antonio
A
Perez-Aytes
Antonio
A
Cortina
Hector
H
Bonafé
Luisa
L
Boccone
Loredana
L
Setzu
Valeria
V
Dutoit
Michel
M
Sangiorgi
Luca
L
Pecora
Fabio
F
Reicherter
Kerstin
K
Nishimura
Gen
G
Spranger
Jürgen
J
Zabel
Bernhard
B
Superti-Furga
Andrea
A
D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental / Q000201:enzymology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism; D004413:Dysostoses / Q000201:enzymology* / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D006811:Humerus / Q000002:abnormalities; D007231:Infant, Newborn; D004204:Joint Dislocations / Q000151:congenital* / Q000201:enzymology / Q000235:genetics*; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000201:enzymology / Q000235:genetics; D010641:Phenotype; D013131:Spine / Q000002:abnormalities; D015238:Sulfotransferases / Q000172:deficiency* / Q000235:genetics*; D013577:Syndrome; D000097811:Carbohydrate Sulfotransferases
D011508:Chondroitin Sulfate Proteoglycans; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases