A novel PLOD1 gene mutation

yphoscoliotic Ehlers-Danlos syndrome (kEDS) is a rare autosomal recessive connective tissue disorder characterized by progressive kyphoscoliosis, congenital muscular hypotonia, marked joint hypermobility, and severe skin hyperextensibility and fragility. Deficiency of lysyl hydroxylase 1 (LH1) due to mutations of PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) gene has been identified as the pathogenic cause of kEDS (kEDS-PLOD1). Up to now, kEDS-PLOD1 has not been reported among Chinese population. We reported a 17-year-old Chinese male patient presenting with hypotonia, joint hypermobility and scoliosis was referred to our hospital. After birth, he was found to have severe hypotonia leading to delayed motor development. Subsequently, joint hypermobility, kyphoscoliosis and amblyopia were found. Inguinal hernia was found at age 5 years and closed by surgery. At the same time, he presented with hyperextensible and bruisable velvety skin with widened atrophic scarring after minor trauma. Dislocation of elbow joint was noted at age of 6 years. Orthopedic surgery for correction of kyphoscoliosis was performed at age 10 years. His family history was unremarkable. Physical examination revealed elevated blood pressure. Slight facial dysmorphologies including high palate, epicanthal folds, and down-slanting palpebral fissures were found. He also had blue sclerae with normal hearing. X-rays revealed severe degree of scoliosis and osteopenia. The Echocardiography findings were normal. Laboratory examination revealed a slightly elevated bone turnover. Based on the clinical manifestations presented by our patient, kEDS was suspected. Genetic analysis revealed a novel homozygous missense mutation of PLOD1 (c.1697 G>A, p.C566Y) (NM_000302.4), confirming the diagnosis of kEDS-PLOD1. Corresponding heterozygous mutation was detected in his parents. This variant is possibly causative for kEDS because it was predicted to be “PROBABLY DAMAGING” with a score 0.999 by Polyphen‐2, “AFFECT PROTEIN FUNCTION” with a score 0.00 by SIFT, and “disease causing” by Mutation Taster.脊柱后侧凸型埃勒斯-当洛斯综合征（kyphoscoliotic Ehlers-Danlos syndrome, kEDS）是一种罕见的常染色体隐性遗传性结缔组织疾病，以进行性脊柱后侧凸、先天性肌张力低下、显著关节过度活动，以及严重皮肤过度伸展和脆性增加为特征。因PLOD1（原胶原-赖氨酸，2-氧戊二酸5-双加氧酶1, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1）基因突变导致的赖氨酰羟化酶1（lysyl hydroxylase 1, LH1）缺乏，已被证实为kEDS-PLOD1型的致病原因。截至目前，中国人群中尚未见kEDS-PLOD1型的相关报道。本文报告1例因肌张力低下、关节过度活动及脊柱侧凸就诊我院的17岁中国男性患者。患者出生后即出现严重肌张力低下，导致运动发育迟缓；后续相继出现关节过度活动、脊柱后侧凸及弱视。5岁时发现腹股沟疝并接受手术修补；同期可见皮肤过度伸展、易挫伤呈天鹅绒样外观，轻微外伤后可形成宽大萎缩性瘢痕。6岁时出现肘关节脱位；10岁时接受脊柱后侧凸矫形骨科手术。患者家族史无异常。体格检查显示血压升高，存在轻微面部畸形：高腭弓、内眦赘皮及睑裂下斜；巩膜呈蓝色，听力正常。X线检查提示严重脊柱侧凸及骨质减少。超声心动图结果未见异常。实验室检查显示骨转换指标轻度升高。结合患者临床表现，疑似kEDS。基因分析检出PLOD1基因新发纯合错义突变（c.1697 G>A, p.C566Y）（NM_000302.4），确诊为kEDS-PLOD1型；其父母均检出相应的杂合突变。经Polyphen-2预测该变异得分为0.999，归类为"PROBABLY DAMAGING"；SIFT预测得分为0.00，归类为"AFFECT PROTEIN FUNCTION"；Mutation Taster则预测其为"disease causing"，提示该变异可能为kEDS的致病突变。