Akalın Akçahan, Özşin Cansu, Koç Nagihan, Demir Gizem Ürel, Alanay Yasemin, Utine Eda, Boduroğlu Koray, Tekçiçek Meryem, Şimşek-Kiper Pelin Özlem
Department of Pediatric Genetics, Department of Pediatrics, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
Department of Pediatric Dentistry, Hacettepe University, Faculty of Dentistry, Ankara, Turkey.
Eur J Med Genet. 2023 Apr;66(4):104708. doi: 10.1016/j.ejmg.2023.104708. Epub 2023 Jan 30.
Genetic skeletal disorders are clinically and genetically heterogeneous group of disorders that affect the normal development, growth, and maintenance of the human skeleton. Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (SMED-SL/AC; MIM# 271665) is a rare autosomal recessive genetic skeletal disorder characterized by distinctive facial features, disproportionate short stature, vertebral, metaphyseal, and epiphyseal abnormalities. This unique phenotype is caused by biallelic loss-of-function variants in Discoidin domain receptor 2 gene (DDR2, MIM# 191311). To date, only 10 pathogenic variants (six missense, two nonsense, one deletion, and one splice site) in DDR2 have been reported in patients with SMED-SL/AC. Dental anomalies related to skeletal dysplasia can include various abnormalities in the number, shape, and position of teeth in the jaw, as well as enamel hypoplasia and dentinogenesis imperfecta. Although abnormal dentition has previously been reported, orodental findings were described in only six patients with SMED-SL/AC. This study aimed to define the clinical, dental, radiological, and molecular findings of three new SMED-SL/AC patients from three unrelated families. Three DDR2 variants, two of which were novel, were detected with the aid of Sanger sequencing. Interestingly, one of the patients was diagnosed with Wilson's disease (WD) during the follow-up, a co-occurrence that has never been reported in patients with SMED-SL/AC so far.
遗传性骨骼疾病是一组临床和遗传异质性疾病，会影响人体骨骼的正常发育、生长和维持。脊椎-干骺端发育不良，短肢-异常钙化型（SMED-SL/AC；MIM# 271665）是一种罕见的常染色体隐性遗传性骨骼疾病，其特征为独特的面部特征、身材比例失调、脊柱、干骺端和骨骺异常。这种独特的表型是由盘状结构域受体2基因（DDR2，MIM# 191311）的双等位基因功能丧失变异引起的。迄今为止，在SMED-SL/AC患者中仅报道了DDR2基因的10种致病变异（6种错义变异、2种无义变异、1种缺失变异和1种剪接位点变异）。与骨骼发育不良相关的牙齿异常可包括颌骨中牙齿数量、形状和位置的各种异常，以及釉质发育不全和牙本质形成不全。尽管此前已有异常牙列的报道，但仅对6例SMED-SL/AC患者的口腔牙齿表现进行了描述。本研究旨在明确来自三个无关家庭的三名新的SMED-SL/AC患者的临床、牙齿、放射学和分子学表现。借助桑格测序检测到三个DDR2变异，其中两个是新发现的变异。有趣的是，其中一名患者在随访期间被诊断出患有威尔逊病（WD），这种共病情况在迄今为止的SMED-SL/AC患者中从未有过报道。
