Phenotypic expansion illuminates multilocus pathogenic variation.
作者： Ender Karaca , Jennifer E Posey , Zeynep Coban Akdemir , Davut Pehlivan , Tamar Harel
DOI: 10.1038/GIM.2018.33
关键词:
摘要: Multilocus variation—pathogenic variants in two or more disease genes—can potentially explain the underlying genetic basis for apparent phenotypic expansion cases which observed clinical features extend beyond those reported association with a “known” gene. Analyses focused on 106 patients, 19 whom was previously attributed to variation at known genes. We performed retrospective computational reanalysis of whole-exome sequencing data using stringent Variant Call File filtering criteria determine whether molecular diagnoses involving additional loci might expanded phenotypes. identified 31.6% (6/19) families and 2.3% (2/87) without expansion. Intrafamilial variability within explained by multilocus severely affected sibling. Our findings underscore role multiple rare different etiology genetically clinically heterogeneous cohorts. genotypic allowed dissection genotype–phenotype relationships families. emphasize critical clinician diagnostic genomic analyses demonstrate that may represent blended phenotypes resulting from pathogenic than one locus.
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