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Spondyloepimetaphyseal dysplasia with joint laxity (Beighton type); mutation analysis in eight affected South African families
Author(s) -
Vorster A.A.,
Beighton P.,
Ramesar R.S.
Publication year - 2015
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12413
Subject(s) - genetics , proband , mutation , osteogenesis imperfecta , phenotype , compound heterozygosity , joint hypermobility , biology , gene , anatomy
Spondyloepimetaphyseal dysplasia with joint laxity (SEMD‐JL), type 1 is an autosomal recessive disorder which has been identified in more than 30 affected children in the Afrikaans‐speaking community of South Africa. Sequencing of B3GALT6 revealed a specific mutation, c.235A > G, in homozygous form in four families, while three others were compound heterozygotes for this mutation in combination with the c.200C > T mutation. In addition, a proband from one family carried the c.16C > T mutation combined with c.200C > T. In a series of five Iranian persons, mutations in B3GALT6 have been implicated in a syndrome characterised by skeletal abnormalities with intellectual disability, bone and connective tissue fragility. Other mutations in B3GALT6 resulted in the classical SEMD‐JL phenotype in seven Japanese families and in a syndrome which has been likened to a progeroid form of Ehlers–Danlos syndrome (EDS). It is evident that there is considerable intragenic heterogeneity in B3GALT6 . One of the mutations, c.200C > T, in the affected South Africans was also present in one of the Japanese persons and the respective phenotypes were identical. The multiplicity of allelic mutations and the phenotypic differences in the affected persons supports the concept that a spectrum of connective tissue disorders is programmed by mutations in B3GALT6 .