Guo Michael H, Shen Yiping, Walvoord Emily C, Miller Timothy C, Moon Jennifer E, Hirschhorn Joel N, Dauber Andrew
Department of Genetics, Harvard Medical School, Boston, Mass., USA.
Horm Res Paediatr. 2014;82(1):44-52. doi: 10.1159/000360857. Epub 2014 Jun 20.
BACKGROUND/AIMS: Short stature is a common reason for presentation to pediatric endocrinology clinics. However, for most patients, no cause for the short stature can be identified. As genetics plays a strong role in height, we sought to identify known and novel genetic causes of short stature.
We recruited 14 children with severe short stature of unknown etiology. We conducted whole exome sequencing of the patients and their family members. We used an analysis pipeline to identify rare non-synonymous genetic variants that cause the short stature.
We identified a genetic cause of short stature in 5 of the 14 patients. This included cases of floating-harbor syndrome, Kenny-Caffey syndrome, the progeroid form of Ehlers-Danlos syndrome, as well as 2 cases of the 3-M syndrome. For the remaining patients, we have generated lists of candidate variants.
Whole exome sequencing can help identify genetic causes of short stature in the context of defined genetic syndromes, but may be less effective in identifying novel genetic causes of short stature in individual families. Utilized in the clinic, whole exome sequencing can provide clinically relevant diagnoses for these patients. Rare syndromic causes of short stature may be underrecognized and underdiagnosed in pediatric endocrinology clinics.
背景/目的：身材矮小是儿童内分泌科门诊常见的就诊原因。然而，对于大多数患者而言，无法确定身材矮小的病因。由于遗传学在身高方面起着重要作用，我们试图确定已知的和新发现的身材矮小的遗传病因。
我们招募了14名病因不明的严重身材矮小儿童。我们对患者及其家庭成员进行了全外显子组测序。我们使用分析流程来识别导致身材矮小的罕见非同义遗传变异。
我们在14名患者中的5名中确定了身材矮小的遗传病因。这包括浮动港综合征、肯尼-卡菲综合征、早老型埃勒斯-当洛综合征的病例，以及2例3-M综合征。对于其余患者，我们列出了候选变异清单。
全外显子组测序有助于在特定遗传综合征背景下识别身材矮小的遗传病因，但在识别个别家庭中身材矮小的新遗传病因方面可能效果较差。在临床中应用，全外显子组测序可为这些患者提供临床相关诊断。身材矮小的罕见综合征病因在儿童内分泌科门诊可能未得到充分认识和诊断。
