Nakamura Sayuri, Kuroki Yoko, Pak Kyongsun, Kamimaki Tsutomu, Mochizuki Takahiro, Ishiguro Akira, Fukami Maki
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
Center for Postgraduate Education and Training, National Center for Child Health and Development, Tokyo, Japan.
Cytogenet Genome Res. 2025;165(2):51-56. doi: 10.1159/000545736. Epub 2025 Jun 13.
Idiopathic short stature (ISS) refers to non-syndromic growth failure without chronic disorders. The molecular basis of ISS remains largely unknown. Although a variable number of tandem repeats (VNTR) of 57 nucleotides in ACAN is known to correlate with the height of people in the general population, the role of this genetic variant in the etiology of ISS has not been studied.
We studied 128 Japanese patients with ISS, including 63 patients with prenatal and postnatal growth failure (small-for-gestational age-SS [SGA-SS]), and 100 control individuals. To examine the repeat numbers of ACAN VNTR, we amplified the VNTR-containing genomic region and analyzed the PCR products by gel electrophoresis. The accuracy of the results was confirmed by long-read next-generation sequencing.
The repeat numbers of the patient group were similarly distributed to those of the control group, and no patient had a very small number. Moreover, the repeat numbers of the shorter and longer alleles in each individual, as well as the average number of the two alleles, were comparable between the two groups. The height standard deviation scores obtained from 106 patients did not correlate with the repeat numbers. There was no difference in the repeat numbers between the SGA-SS or non-SGA ISS groups, and the control group.
The results of this study indicate that reduced repeat numbers of ACAN VNTR do not represent a monogenic cause or a major contributing factor for ISS. Our findings await further validation.
特发性身材矮小（ISS）是指无慢性疾病的非综合征性生长发育迟缓。ISS的分子基础在很大程度上仍不清楚。虽然已知ACAN基因中57个核苷酸的可变串联重复序列（VNTR）数量与普通人群的身高相关，但该基因变异在ISS病因学中的作用尚未得到研究。
我们研究了128例日本ISS患者，其中包括63例产前和产后生长发育迟缓患者（小于胎龄儿-身材矮小[SGA-SS]），以及100名对照个体。为检测ACAN VNTR的重复次数，我们扩增了包含VNTR的基因组区域，并通过凝胶电泳分析PCR产物。结果的准确性通过长读长下一代测序得以证实。
患者组的重复次数分布与对照组相似，且没有患者的重复次数非常少。此外，两组个体中较短和较长等位基因的重复次数以及两个等位基因的平均次数相当。106例患者的身高标准差得分与重复次数无关。SGA-SS组或非SGA ISS组与对照组之间的重复次数没有差异。
本研究结果表明，ACAN VNTR重复次数减少并非ISS的单基因病因或主要促成因素。我们的研究结果有待进一步验证。
