Department of Endocrinology.
Department of Genetics and Metabolism, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
Medicine (Baltimore). 2021 Mar 19;100(11):e25169. doi: 10.1097/MD.0000000000025169.
X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is a rare hereditary cause in childhood short stature due to mutations in trafficking protein particle complex subunit 2 (TRAPPC2) gene located on chromosome Xp22. Several pathogenic variants in TRAPPC2 have been reported, but missense variants are rare.
A 13-year, 8-month-old Chinese Han boy presenting with short stature for the past 7 years.
X-linked SEDT was established by a combination of clinical and radiographic features, confirmed by targeted next-generation sequencing. Genetic testing of the TRAPPC2 gene revealed a novel missense variant with c.260A>C (p.H87P) hemizygote in exon5. The mother was found to be a heterozygous TRAPPC2 carrier, whereas the father was normal.
Patient was treated with recombinant human growth hormone daily. Patient's height, glucose level, and possible progressive joint and back pain with osteoarthritis were under intensive observation regularly.
The patient achieved 2.1 cm height gain over the first 3 months' recombinant human growth hormone treatment without joint or back pain. However, the therapy was terminated because of increased glucose level on follow-up.
The short stature is a noteworthy problem for X-linked SEDT cases. We report a novel missense variant site in TRAPPC2 treated with growth hormone in the literature. We do not recommend the use of recombinant human growth hormone on patients with X-linked SEDT for the concern of glucose homeostasis.
X 连锁迟发性脊椎骨骺发育不良（X-linked SEDT）是一种罕见的遗传性儿童身材矮小疾病，由于位于 Xp22 染色体上的运输蛋白颗粒复合物亚基 2（TRAPPC2）基因突变所致。TRAPPC2 中已报道了几种致病变体，但错义变体很少见。
一名 13 岁 8 个月大的中国汉族男孩，过去 7 年来一直身材矮小。
通过临床和影像学特征的综合表现，结合靶向下一代测序，确定为 X 连锁 SEDT。TRAPPC2 基因的遗传检测显示外显子 5 中存在一种新型错义变体 c.260A>C（p.H87P）半合子。母亲被发现是 TRAPPC2 的杂合子携带者，而父亲是正常的。
患者接受了重组人生长激素的每日治疗。患者的身高、血糖水平以及可能出现的关节炎进展性关节和背部疼痛，都在密切观察下定期进行。
患者在接受重组人生长激素治疗的前 3 个月身高增加了 2.1cm，没有关节或背部疼痛。然而，由于随访时血糖升高，治疗被终止。
身材矮小是 X 连锁 SEDT 病例的一个显著问题。我们报告了一个新的 TRAPPC2 错义变体部位，该变体在文献中接受了生长激素治疗。由于对葡萄糖稳态的担忧，我们不建议对 X 连锁 SEDT 患者使用重组人生长激素。
