一例X连锁点状软骨发育不全2型患儿的临床及突变分析

Analysis of clinical manifestation and genetic mutation in a child with X-linked chondrodysplasia punctata 2

目的分析1例重度矮小合并畸形患儿的临床特点及基因变异，探讨其遗传学病因。方法对患儿进行病史采集和辅助检查，提取患儿及其部分家系成员的外周血基因组DNA，用Agilent SureSelect方法构建测序文库，在Illumina平台上进行高通量测序，并用Sanger测序法进行验证。结果患儿，女，6岁10个月，表现为非匀称性身材矮小、特殊面容、四肢及脊柱畸形，左眼弱视，右眼白内障，呼吸道频发感染，尿频等，实验室检查提示总25-羟维生素D缺乏，其母亲、姨妈、弟弟亦表现为身材矮小。基因检测显示患儿EBP基因存在C．184C〉T（p．Arg62Trp）杂合突变，其母亲携带同样的突变，父亲和弟弟则未发现该突变。结论EBP基因C．184C〉T（p．Arg62Trp）杂合突变可能是该家系的发病原因。

Objective To analyze clinical manifestations and genetic mutation in a child with severe short stature and other malformations. Methods The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples of the proband and her family members. Candidate genes were captured with Agilent SureSelect and sequenced on an Illumina platform. Suspected mutation was verified by Sanger sequencing. Results The patient, a six-year-and-10-month old girl, presented with non-symmetrical short stature, dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and cataract of right eye, in addition with frequent respiratory infection and micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency （18. 9 ng/mL）. Spine X-ray showed multiple malformations with centrums. Her mother also featured short stature （138 cm）. Her aunt had short stature （130 cm） and limb-length discrepancy. Her little brother was 2.5 years old, and his height was 81 cm （-3.4 SD）. Exome sequencing revealed a heterozygous mutation c. 184C〉T （p. Arg62Trp） in the proband and her mother. The same mutation was not found in her father and brother. Conclusion The patient was diagnosed with X-linked chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the disease in this family.