Das Liza, Dhiman Vandana, Van Hul Wim, Bhansali Anil, Gogate Yashpal, Steenackers Ellen, Mortier Geert, Bhadada Sanjay Kumar
Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER) Chandigarh, India.
Department of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
Bone Rep. 2020 Jan 11;12:100245. doi: 10.1016/j.bonr.2020.100245. eCollection 2020 Jun.
Spondylo-epi-metaphyseal dysplasia (SEMD) represents a group of osteo-chondrodysplasias characterized by vertebral, epiphyseal as well as metaphyseal abnormalities. Several genes have been identified underlying the different forms.
Two relatives (cousins) in a family were found to have disproportionate short stature with clinical and radiological features suggestive of SEMD. Metabolic bone profile was normal including parathyroid hormone and 25(OH)vitamin D3. Exome sequencing revealed a missense mutation (p. T120M) in the von-Willebrand factor A-domain of the Matrilin 3 () gene that segregates with the disease in the family.
We identified a homozygous missense mutation in , an important structural component of the extracellular matrix of cartilage, as the genetic cause of SEMD in this pedigree. mutations have been more commonly associated with multiple epiphyseal dysplasia than SEMD. Recognition of this mutation will aid in enhancing the understanding and expanding the spectrum of this particular skeletal dysplasia.
脊椎骨骺干骺端发育不良（SEMD）是一组骨软骨发育不良，其特征为椎体、骨骺以及干骺端异常。已确定多种不同形式的潜在致病基因。
在一个家族中发现两名亲属（表亲）身材比例失调，具有提示SEMD的临床和放射学特征。代谢性骨指标正常，包括甲状旁腺激素和25（OH）维生素D3。外显子组测序显示，基质金属蛋白酶3（MATN3）基因的血管性血友病因子A结构域存在错义突变（p.T120M），该突变在家族中与疾病共分离。
我们在软骨细胞外基质的重要结构成分MATN3中鉴定出一个纯合错义突变，作为该家系中SEMD的遗传病因。MATN3突变与多发性骨骺发育不良的关联比与SEMD更为常见。识别该突变将有助于增进对这种特殊骨骼发育不良的理解并扩大其疾病谱。
