Analysis of a Chinese pedigree affected with familial short stature due to 15q25.3q26.1 deletion involving theACAN gene
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目的 探讨1个矮小家系的遗传学病因，为临床诊断及制定治疗策略提供参考。 方法 选取2020年7月在宁波市妇女儿童医院确诊为家族性矮小(FSS)的1例患儿及其父母、祖父母以及外祖父母为研究对象。收集先证者及其上述家系成员的临床资料，采集外周血样，提取基因组DNA，对先证者进行全外显子组测序(WES)，对先证者及其父母、祖父母进行染色体微阵列分析(CMA)，采用重组人生长激素(rhGH)对先证者进行治疗并评估效果。 结果 先证者身高为87.7 cm(-3 s)，其父亲身高为152 cm(-3.39 s)，母亲及祖父母身高无明显异常。WES提示先证者染色体15q25.3-q26.1区存在4.35 Mb缺失，CMA提示先证者及其父亲15号染色体长臂均存在4.342 Mb的杂合缺失[arr[hg19]15q25.3-q26.1(86828614_91170208)×1]，该缺失片段涉及与矮小表型密切相关的ACAN基因。母亲及祖父母CMA检测均未见异常。上述缺失在人群数据库及相关文献中均未见报道，根据美国医学遗传学与基因组学学会(ACMG)相关指南，评估为致病性拷贝数变异。用rhGH治疗14个月后，先证者身高增加至98.5 cm(-2.07 s)，疗效显著。 结论 涉及ACAN基因的染色体15q25.3-q26.1微缺失可能导致FSS，短期rhGH治疗可有效改善这类患儿的身高。 Objective To analyze the genetic etiology of a Chinese pedigree affected with short stature. Methods A child with familial short stature (FSS) who had presented at the Ningbo Women and Children′s Hospital in July 2020 and his parents and paternal and maternal grandparents were selected as the study subjects. Clinical data of the pedigree was collected, and the proband was subjected to routine growth and development assessment. Peripheral blood samples were collected. The proband was subjected to whole exome sequencing (WES), and the proband, his parents and grandparents were subjected to chromosomal microarray analysis (CMA). Results The height of the proband and his father was 87.7cm (-3 s) and 152 cm (-3.39 s) respectively. Both of them were found to harbor a 15q25.3-q26.1 microdeletion, which has encompassed the whole of the ACAN gene which is closely associated with short stature. The CMA results of his mother and grandparents were all negative, and above deletion has not been included in population database and related literature, and was rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). After 14 months of rhGH treatment, the height of the proband has increased to 98.5 cm (-2.07 s). Conclusion The 15q25.3-q26.1 microdeletion probably underlay the FSS, in this pedigree. Short-term rhGH treatment can effectively improve the height of the affected individuals.
Objective To analyze the genetic etiology of a Chinese pedigree affected with short stature. Methods A child with familial short stature (FSS) who had presented at the Ningbo Women and Children′s Hospital in July 2020 and his parents and paternal and maternal grandparents were selected as the study subjects. Clinical data of the pedigree was collected, and the proband was subjected to routine growth and development assessment. Peripheral blood samples were collected. The proband was subjected to whole exome sequencing (WES), and the proband, his parents and grandparents were subjected to chromosomal microarray analysis (CMA). Results The height of the proband and his father was 87.7cm (-3 s) and 152 cm (-3.39 s) respectively. Both of them were found to harbor a 15q25.3-q26.1 microdeletion, which has encompassed the whole of the ACAN gene which is closely associated with short stature. The CMA results of his mother and grandparents were all negative, and above deletion has not been included in population database and related literature, and was rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). After 14 months of rhGH treatment, the height of the proband has increased to 98.5 cm (-2.07 s). Conclusion The 15q25.3-q26.1 microdeletion probably underlay the FSS, in this pedigree. Short-term rhGH treatment can effectively improve the height of the affected individuals.
Chromosome deletionACAN geneFamilial short statureGrowth hormone
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