Comprehensive analysis of clinical spectrum and genotype associations in Chinese and literature reported KBG syndrome
Qiuyue Li, Chengjun Sun, Lin Yang, Wei Lu, Feihong Luo
Abstract
BACKGROUND: gene variant types, the 16q24.3 microdeletion, and the clinical spectrum of KBG syndrome. METHODS: The genetic etiology of three unreported KBG patients was identified by whole exome sequencing and confirmed via Sanger sequencing. Literature review was conducted to summarize the phenotype-genotype relationship based on three unreported Chinese cases and 186 reported cases. RESULTS: gene mutations showed significantly higher frequency of malformations including macrodontia, long philtrum, abnormal eyebrows, widely spaced eyes, anteverted nares, eyelid ptosis, brachydactyly, brachycephaly (P<0.05), and significantly lower risk of congenital heart diseases and frontal bossing (P<0.05). The intellectual disability (ID) was significantly milder among patients carrying truncating variants located between repression domain 1 (RD1) and activation domain (AD) than those carrying mutations disrupting repression domain 2 (RD2) alone and disrupting all functional domain (RD1, AD or RD2) (P<0.05). CONCLUSIONS: gene variants disrupting RD1 and RD2 or RD2 alone are more likely to have more severe ID, which warrants different intervention strategies for KBG syndrome.