Publication Type:

Journal Article

Source:

Human Mutation, Volume 31, Number 11, p.1233-1239 (2010)

URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-78049440754&partnerID=40&md5=a5e11ff3c0a200ca5ce786804e3a0d4b

Keywords:

Abnormalities, adducted thumb clubfoot syndrome, adolescent, article, Base Sequence, case report, child, CHST14 gene, clubfoot, collagen, Complementary, consanguinity, Contracture, dermatan, dermatan 4 sulfotransferase 1, DNA, DNA Mutational Analysis, Ehlers Danlos syndrome, Ehlers-Danlos Syndrome, electron microscopy, female, frameshift mutation, gene, gene mutation, Genes, homozygosity, human, Humans, Indian, Insertional, joint contracture, kyphoscoliosis, loss of function mutation, male, Multiple, muscle hypotonia, Mutagenesis, nucleotide sequence, Pedigree, phenotype, priority journal, pyridinoline, Recessive, sequence analysis, Sequence Deletion, single nucleotide polymorphism, skin manifestation, sulfotransferase, Sulfotransferases, thumb, unclassified drug, wrinkle, Young Adult

Abstract:

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 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, 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.Val49z.ast;) 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.Glu334Glyfsz.ast;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 forms a clinical spectrum, which we propose to coin as "musculocontractural EDS" and which results from a defect in dermatan sulfate biosynthesis, perturbing collagen assembly.Hum Mutat 31:1-7, 2010. © 2010 Wiley-Liss, Inc.

Notes:

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Cite this Research Publication

Fa Malfait, Syx, Da, Vlummens, Pa, Symoens, Sa, Nampoothiri, Sb, Hermanns-Lê, Tc, Van Laer, La, and De Paepe, Aa, “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”, Human Mutation, vol. 31, pp. 1233-1239, 2010.