ACAN基因变异致矮身材基因改变与临床观察

Gene Mutation and Its Clinical Observation of Short Stature Caused by ACAN Gene Mutation

摘要: 目的：分析ACAN基因变异与矮身材的关系，观察重组人生长激素(rhGH)的疗效与安全性。方法：回顾分析一例ACAN基因变异的矮身材患儿的临床资料，检索相关文献，总结ACAN基因变异与矮身材的关系，观察rhGH的疗效与安全性。结果：患儿为5岁7个月的女孩，矮身材，身高104.7 cm (−2.22 SD)，其父亲身高175 cm (+0.42 SD)，母亲身高163 cm (+0.47 SD)，家族中均无矮身材者；无特殊面容及骨骼畸形，无第二性征发育；骨龄示7岁；基因测序示ACAN基因存在杂合变异c534C > G (p.N178K)，其父母该位点均无变异，其为自发突变。予rhGH 50 ug∙kg⁻¹∙d⁻¹治疗，身高第一年增长7.8 cm (112.5 cm, −1.58 SD)，后予rhGH 60 ug∙kg⁻¹∙d⁻¹治疗8个月，身高增长4.9 cm (117.4 cm, −1.28 SD)，身高由−2.22SD追至−1.28 SD；骨龄进展2.5岁。结论：骨龄提前的矮身材患儿应考虑存在ACAN基因突变；应用rhGH治疗身高明显改善。

Abstract: Objective: To analyze the relationship between ACAN gene variation and short stature and observe the efficacy and safety of recombinant human growth hormone (rhGH). Methods: Review the clinical data of a case of idiopathic short stature with ACAN gene mutation and search the relevant literatures to summarize the relationship between ACAN gene mutation and short stature, and observe the efficacy and safety of recombinant human growth hormone. Results: The patient was a 5-year and 7 months old girl with a short stature of 104.7 cm (−2.22 SD). She had short stature and was 104.7 cm (−2.22 SD) in height. Her father was 175 cm (+0.42 SD) in height and her mother was 163 cm (+0.47 SD) in height .There was no short stature in her family. There was no special face and skeletal deformity and secondary sexual development. Her bone age was 7 years. The gene sequencing revealed a heterozygous variation (c534c > G (p.n178k)) in ACAN gene, which was spontaneous mutation. And there was no mutation in this locus of the ACAN gene in her parents. Her height increased by 7.8 cm (112.5 cm, −1.28 SD) in the first year of treatment with rhGH (50 ug∙kg⁻¹∙d⁻¹) and the height increased by 4.9 cm (117.4 cm, −1.28SD) after 8 months of treatment with rhGH (60 ug∙kg⁻¹∙d⁻¹). Her height recovered from −2.22 SD to −1.28 SD and her bone age progressed by 2.5 years. Conclusion: The ACAN gene mutation should be considered in children with advanced bone age and the height can be improved significantly by rhGH.