重组人生长激素改善ACAN基因变异致家族性矮小的疗效观察及文献复习

目的观察重组人生长激素(rhGH)改善ACAN基因变异致家族性矮小患者身高的疗效。方法回顾分析2个ACAN基因变异致家族性矮小家系rhGH治疗的临床资料,并检索相关文献进行分析。结果先证者1,男,4岁1个月,身高90.5 cm(-3.6 SD),体质量13.5 kg,无明显骨骼畸形;骨龄示5岁6个月龄;基因检测示ACAN基因c.5026_5027del(p.Ser 1676 Ter)杂合缺失变异;予rhGH,50μg/(kg·d)治疗,第1年身高增加13 cm(103.5 cm,-1.8 SD),至第18个月身高增加17.1 cm(107.6 cm,-1.7 SD)。先证者2,男,3岁,身高82 cm(-3.9 SD),体质量12 kg,无明显骨骼畸形;骨龄示1岁6个月龄;基因检测示ACAN基因c.1504C>T(p.R 502C)杂合错义变异;予rhGH,33μg/(kg·d)治疗,第1年身高增加12 cm(94.0 cm,-2.6 SD),至第22个月身高增加17 cm(99.0 cm,-2.68 SD)。结论ACAN基因c.5026_5027 del杂合缺失变异以及c.1504C>T错义变异可引起家族性矮小;rhGH治疗短期可有效改善ACAN基因致家族性矮小患儿的身高。

Efficacy of recombinant human growth hormone therapy in familial short stature with ACAN gene variants and review of literature

Objective ACAN gene is one of the most frequently mutated genes in familial short stature(FSS),which has key roles in endochondral ossification and maintaining the biological function of cartilage.To observe the efficacy of recombinant human growth hormone(rhGH)for increasing the height of children of FSS with ACAN gene variants.Methods Clinical data obtained from 2 pedigrees of FSS caused by ACAN gene variants at our institution were retrospectively analyzed.Relevant electronic databases were searched for studies assessing the therapeutic effect of rhGH in children of FSS with ACAN gene variants.Results The proband of family 1 was a 4-year and 1-month-old boy and without skeletal deformity,when his height was 90.5cm(-3.6 SD)and weight 13.5 kg.His bone age was 5 years and 6 months.Genetic testing identified a heterozygous deletion mutation in ACAN gene(c.5026_5027 del,p.Ser 1676 Ter).His height increased by 13 cm(Ht:103.5 cm,-1.8 SD)in the first year of treatment with rhGH(50μg·kg-1·d-1)and height increased by 17.1 cm(Ht:107.6 cm,-1.7 SD)after 18 months of treatment.The proband of family 2 was a 3-year-old boy without skeletal deformity,when his height was 82cm(-3.9 SD)and weight 12 kg.His bone age was 1 year and 6 months.Genetic testing identified a heterozygous missense mutation in ACAN gene(c.1504C>T,p.R502C).His height increased by 12cm(Ht:94cm,-2.6 SD)in the first year of treatment with rhGH(33μg·kg-1·d-1)and height increased by 17 cm(Ht:99 cm,-2.68 SD)after 22 months of treatment.Conclusion Heterozygous deletion mutation(c.5026_5027 del)and heterozygous missense mutation(c.1504 C>T)of ACAN gene can cause FSS.rhGH therapy can effectively improve the height of children of FSS with ACAN gene variants in the short term.It is recommended to detect gene in patients of FSS and to treat the disease with rhGH as early as possible.