PDF(Pubmed)
Abstract：
UNASSIGNED: Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is limited genetic research on exome sequencing for short stature, and more large-scale studies are necessary for further exploration.
UNASSIGNED: The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ -2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures.
UNASSIGNED: The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome.
UNASSIGNED: WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.
UNASSIGNED: The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ -2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures.
UNASSIGNED: The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome.
UNASSIGNED: WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.
摘要：
■身材矮小是儿童最常见的内分泌失调之一，其遗传基础是一个复杂而积极研究的课题。目前,对身材矮小的外显子组测序的遗传研究有限，更大规模的研究需要进一步探索。
这项回顾性研究涉及对2017年至2021年间招募的98名不明病因的身材矮小（身高SDS≤-2.5）中国儿童进行调查。对这些患者进行全外显子组测序（WES）以确定潜在的遗传病因。回顾性回顾了临床数据，以评估已鉴定突变的致病性。此外,31例患者同意并接受重组人生长激素（rhGH）治疗12个月。对身材矮小患者的不同病因评估了rhGH治疗的短期效果。
■WES结果用于在24（24.5％）患者中鉴定18个基因中的31个不同变体。身材矮小的个体更有可能具有潜在的遗传病因。与简单的严重身材矮小相比，伴有其他表型的身材矮小的诊断率明显更高。rhGH治疗在大多数儿童中显示出疗效。然而，在一名被诊断为3M综合征的男孩中，治疗反应欠佳。
■WES是确认病因不明的重度矮小患者遗传疾病的重要方法。这表明它可以用作主要的诊断策略。rhGH的给药可能不适合所有身材矮小的儿童，通过WES鉴定矮小的遗传原因对rhGH治疗具有重要的指导价值。
这项回顾性研究涉及对2017年至2021年间招募的98名不明病因的身材矮小（身高SDS≤-2.5）中国儿童进行调查。对这些患者进行全外显子组测序（WES）以确定潜在的遗传病因。回顾性回顾了临床数据，以评估已鉴定突变的致病性。此外,31例患者同意并接受重组人生长激素（rhGH）治疗12个月。对身材矮小患者的不同病因评估了rhGH治疗的短期效果。
■WES结果用于在24（24.5％）患者中鉴定18个基因中的31个不同变体。身材矮小的个体更有可能具有潜在的遗传病因。与简单的严重身材矮小相比，伴有其他表型的身材矮小的诊断率明显更高。rhGH治疗在大多数儿童中显示出疗效。然而，在一名被诊断为3M综合征的男孩中，治疗反应欠佳。
■WES是确认病因不明的重度矮小患者遗传疾病的重要方法。这表明它可以用作主要的诊断策略。rhGH的给药可能不适合所有身材矮小的儿童，通过WES鉴定矮小的遗传原因对rhGH治疗具有重要的指导价值。
