Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia

By Long Guo, N. Elcioglu, Shuji Mizumoto, Z. Wang, Bilge Noyan, H. Albayrak, S. Yamada, N. Matsumoto, N. Miyake, G. Nishimura and 1 more. 2017

31 citations recorded by the source corpus.

Spondylo-epi-metaphyseal dysplasia (SEMD) is a group of inherited skeletal diseases characterized by the anomalies in spine, epiphyses and metaphyses. SEMD is highly heterogeneous and >20 distinct entities have been identified. Here we describe a novel type of SEMD in two unrelated Turkish patients who presented with severe platyspondyly, kyphoscoliosis, pelvic distortion, constriction of the proximal femora and brachydactyly. Although these phenotypes overlap considerably with some known SEMDs, they had a novel causal gene, exostosin-like glycosyltransferase 3 (EXTL3), that encodes a glycosyltransferase involved in the synthesis of heparin and heparan sulfate. The EXTL3 mutation identified in the patients was a homozygous missense mutation (c.953C>T) that caused a substitution in a highly conserved amino acid (p.P318L). The enzyme activity of the mutant EXTL3 protein was significantly decreased compared to the wild-type protein. Both patients had spinal cord compression at the cranio-vertebral junction and multiple liver cysts since early infancy. One of the patients showed severe immunodeficiency, which is considered non-fortuitous association. Our findings would help define a novel type of SEMD caused by EXTL3 mutations.

Subfields: Cell Biology, Genetics, Molecular Biology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

  1. H. Sheth
  2. F. Sheth
  3. J. Sheth
  4. S. Bajaj
  5. Purnima S. Satoskar
  6. Aadhira Nair

Citations in the corpus