New developments in the genetic diagnosis of short stature

作者：Jee Youn Hee^*; Baron Jeffrey; Nilsson Ola

来源：Current Opinion in Pediatrics, 2018, 30(4): 541-547.

DOI：10.1097/MOP.0000000000000653

• exome sequencing
• genetic cause
• genome-wide association study
• short stature

Purpose of review
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.
Recent findings
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.
Summary
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.

• 出版日期2018-8
• 单位NIH