Musculo-contractural 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 <i>CHST14 </i>gene. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Human Mutation Année : 2010

Musculo-contractural 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.

Delfien Syx
  • Fonction : Auteur
  • PersonId : 902699
Philip Vlummens
  • Fonction : Auteur
  • PersonId : 902700
Sofie Symoens
  • Fonction : Auteur
  • PersonId : 902701
Trinh Hermanns-Lê
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  • PersonId : 902703
Lut van Laer
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  • PersonId : 902704
Anne Depaepe
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  • PersonId : 885521

Résumé

We present clinical and molecular findings of three patients with an EDS VIB phenotype from two consanguineous families. The clinical findings of EDS kyphoscoliotic type (EDS type VI A&B) comprise kyphoscoliosis, muscular hypotonia, hyperextensible, thin and bruisable skin, atrophic scarring, jointhypermobility and variable ocular involvement. Distinct craniofacial abnormalities, joint contractures, wrinkled 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 sequence analysis of CHST14 identified a homozygous 20-bp duplication (NM_130468.2:c.981_1000dup, NP_569735.1:p.Glu334Glyfs*107) in an Indian patient. Loss-of-function mutations in CHST14 were recently reported in adducted thumb-clubfoot syndrome (ATCS). Patients with ATCS present similar craniofacial and musculoskeletal features as the EDS VIB patients reported here, but lack the severe skin manifestations. By identifying an 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 CHST14 mutations (Miyake, et al., 2010) forms a clinical spectrum, which we propose to coin as "musculo-contractural EDS", and which results from a defect in dermatan sulfate biosynthesis, perturbing collagen assembly.

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Dates et versions

hal-00599478 , version 1 (10-06-2011)

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Fransiska Malfait, Delfien Syx, Philip Vlummens, Sofie Symoens, Sheela Nampoothiri, et al.. Musculo-contractural 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.. Human Mutation, 2010, 31 (11), pp.1233. ⟨10.1002/humu.21355⟩. ⟨hal-00599478⟩

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