Steel syndrome is an autosomal recessive disorder that primarily affects the skeletal system causing a variety of manifestations. Sixteen individuals with Steel syndrome, mainly Puerto Ricans (11/16), were previously reported to carry bi-allelic mutations in the COL27A1 gene. Here, we present the first patient with Steel syndrome in Europe and the sixth non-Puerto Rican carrying a novel homozygous mutation in COL27A1. The patient is a 4-year-old boy born to non-consanguineous healthy parents, with dysmorphic facial features, absent hip ossification centres, external rotation of both feet, relatively short stature, mild skin syndactyly, short mid phalanges and bilateral sensorineural hearing loss. Whole exome sequencing (WES) revealed a novel homozygous missense variant p.(Gly802Glu) in COL27A1. The homozygous mutation was confirmed by Sanger sequencing in the proband and carrier status was confirmed in both parents and his unaffected sibling. According to online and in-house minor allele frequency (MAF) databases, this is the first COL27A1 mutation reported in the European population. Additional screening of healthy Greek-Cypriot individuals was thus performed, which did not reveal any additional carriers in the population for the variant in question.

钢铁综合症是一种常染色体隐性遗传疾病，主要影响骨骼系统并引起多种表现。据报道，先前有16名患有钢铁综合症的人，主要是波多黎各人（11/16），其COL27A1基因携带双等位基因突变。在这里，我们介绍了欧洲的第一例钢综合征患者和第六例携带新的纯合子突变的COL27A1非波多黎各人。该患者是一个4岁男孩，由非血缘健康的父母生，具有畸形的面部特征，无髋骨骨化中心，双脚外旋，身材相对矮小，皮肤轻度综合征，中指骨短和双侧感觉神经性听力减退。整个外显子测序（WES）揭示了一种新的纯合错义变异体第（Gly802Glu）在COL27A1。通过先证者中的Sanger测序证实了纯合突变，并且在父母和他未受影响的兄弟姐妹中均证实了携带者的状态。根据在线和内部的未成年人等位基因频率（MAF）数据库，这是第一个COL27A1欧洲人口中报告有突变。因此，对健康的希族塞浦路斯人进行了额外的筛查，但并未发现该变体在人群中有其他携带者。