Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, USA.
Department of Women's and Children's Health, Karolinska Institutet, Stockholm.
Curr Opin Pediatr. 2018 Aug;30(4):541-547. doi: 10.1097/MOP.0000000000000653.
Genome-wide approaches including genome-wide association studies as well as exome and genome sequencing represent powerful new approaches that have improved our ability to identify genetic causes of human disorders. The purpose of this review is to describe recent advances in the genetic causes of short stature.
In addition to SHOX deficiency which is one of the most common causes of isolated short stature, PAPPA2, ACAN, NPPC, NPR2, PTPN11 (and other rasopathies), FBN1, IHH and BMP2 have been identified in isolated growth disorders with or without other mild skeletal findings. In addition, novel genetic causes of syndromic short stature have been discovered, including pathogenic variants in BRCA1, DONSON, AMMECR1, NFIX, SLC25A24, and FN1.
Isolated growth disorders are often monogenic. Specific genetic causes typically have specific biochemical and/or phenotype characteristics which are diagnostically helpful. Identification of additional subjects with a specific genetic cause of short stature often leads to a broadening of the known clinical spectrum for that condition. The identification of novel genetic causes of short stature has provided important insights into the underlying molecular mechanisms of growth failure.
全基因组关联研究以及外显子组和基因组测序等全基因组方法代表了强大的新方法，提高了我们识别人类疾病遗传原因的能力。本文旨在描述身材矮小遗传原因的最新进展。
除 SHOX 缺乏症（孤立性身材矮小最常见的原因之一）外，PAPPA2、ACAN、NPPC、NPR2、PTPN11（和其他 Ras 相关疾病）、FBN1、IHH 和 BMP2 已在伴有或不伴有其他轻微骨骼表现的孤立性生长障碍中被发现。此外，还发现了综合征性身材矮小的新遗传原因，包括 BRCA1、DONSON、AMMECR1、NFIX、SLC25A24 和 FN1 中的致病性变异。
孤立性生长障碍通常是单基因疾病。特定的遗传原因通常具有特定的生化和/或表型特征，有助于诊断。确定具有特定身材矮小遗传原因的其他患者通常会扩大该疾病的已知临床谱。身材矮小新遗传原因的鉴定为生长障碍的潜在分子机制提供了重要的见解。
