METHODS: We studied 37 family trios where infants had PCG and were part of the National Birth Defects Prevention Study (births 1997-2011), a U.S. multicenter study of birth defects. Samples underwent exome sequencing and sequence reads were aligned to the human reference sample (NCBI build 37/hg19). Variant filtration was conducted under de novo and Mendelian inheritance models using GEMINI.
RESULTS: Among candidate variants, CYP1B1 was most represented (five trios, 13.5%). Twelve probands (32%) had potentially pathogenic variants in other genes not previously linked to PCG but important in eye development and/or to underlie Mendelian conditions with potential phenotypic overlap (e.g., CRYBB2, RXRA, GLI2).
CONCLUSIONS: Variation in the genes identified in this population-based study may help to further explain the genetics of PCG.
方法:我们研究了37个家庭三重奏,其中婴儿患有PCG,并且是国家出生缺陷预防研究的一部分(出生1997-2011),美国出生缺陷多中心研究。样品经历外显子组测序,并将序列读数与人参考样品(NCBI构建37/hg19)进行比对。使用GEMINI在从头和孟德尔遗传模型下进行变体过滤。
结果:在候选变体中,CYP1B1代表最多(五个三重奏,13.5%)。12个先证者(32%)在其他基因中具有潜在的致病性变异,这些基因以前与PCG无关,但在眼睛发育和/或具有潜在表型重叠的孟德尔疾病的基础上很重要(例如,CRYBB2,RXRA,GLI2).
结论:这项基于人群的研究中发现的基因变异可能有助于进一步解释PCG的遗传学。