Musculocontractural Ehlers-Danlos syndrome (Former EDS Type VIB) and Adducted Thumb Clubfoot Syndrome (ATCS) represent a single clinical entity caused by mutations in the Dermatan-4-Sulfotransferase 1 encoding CHST14 gene
[en] We present clinical and molecular findings with three patients with an EDS VIB phenotype from two consanguineous families. The clinical finding of EDS kyphoscoliotic (EDS type VIA and B) comprise kyphoscoliosis, muscular hypotonia, hyperextensible, thin and bruisable skin, atrophic scarring, joint hypermobility, and variable ocular involvement. Distinct craniofacial abnormalities, joint contractures, winkled palms, and normal urinary pyridinoline ratios distinguish EDS VIB from EDS VIA. A genome-wide SNP scan and sequence analyses identified a homozygous frameshift mutation (NM_130468.2:c.145delG, NP_569735.1:p.val49*) in CHST14, encoding dermatan-4- sulfotransferase 1 (D4ST-1), in two Turkish siblings. Subsequent sequences analysis of CHST14 identified a homozygous 20-bp duplication (NM_130468.2:c.981_1000dup, NP_569735.1p.Glu334-Glyfs*107) in an Indian patient. Loss-of-function mutations in CHTS14 were recently reported in adducted thumb clubfoot syndrome (ATCS). Patients with ATCS present similar craniofacial and muscoloskeletal features as the EDS VIB patients reported here, but lack the severe skin manifestations. By identifying the identical mutation in patients with EDS VIB and ATCS, we show that both conditions form a phenotypic continuum. Our findings confirm that the EDS-variant associated with the CHTS14 mutations forms a clinical spectrum, which we propose to coin as "musculocontractural EDS" and which results from a defect in dermatan sulfate biosynthesis, perturbing collagen synthesis.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Malfait, Fransiska; Ghent University Hospital, Belgium > Center for Medical Genetics
Syx, Delfien; Ghent University Hospital, Belgium > Center of Medical Genetics
Vlummens, Philip; Ghent University Hospital, Belgium > Center for Medical Genetics
Symoens, Sofie; Ghent University Hospital, Belgium > Center for Medical Genetics
Nampoothiri, Sheela; Amrita Institute of Medical Sciences and Research Center, Cochin, Kerala, India
Hermanns-Lê, Trinh ; Université de Liège > Département des sciences cliniques > Dermatopathologie
Language :
English
Title :
Musculocontractural Ehlers-Danlos syndrome (Former EDS Type VIB) and Adducted Thumb Clubfoot Syndrome (ATCS) represent a single clinical entity caused by mutations in the Dermatan-4-Sulfotransferase 1 encoding CHST14 gene
Publication date :
14 September 2010
Journal title :
Human Mutation
ISSN :
1059-7794
eISSN :
1098-1004
Publisher :
Wiley Liss, Hoboken, United States - New Jersey
Volume :
31
Issue :
11
Pages :
1233-1239
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Methusalem Grant 08/01M01108 from Ghent University to A.D.P. and Grant G.0171.05 from the Fund for Scientific Research Flanders, Belgium for A.D.P.
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