BACKGROUND We report a large family with four successive generations, presenting with a complex phenotype of severe congenital neutropenia (SCN), partially penetrant monocytosis, and hearing loss of varying severity. METHODS We performed whole exome sequencing to identify the causative variants. Sanger sequencing was used to perform segregation analyses on remaining family members. RESULTS We identified and classified a pathogenic GFI1 variant and a likely pathogenic variant in MYO6 which together explain the complex phenotypes seen in this family. CONCLUSIONS We present a case illustrating the benefits of a broad screening approach that allows identification of oligogenic determinants of complex human phenotypes which may have been missed if the screening was limited to a targeted gene panel with the assumption of a syndromic disorder. This is important for correct genetic diagnosis of families and disentangling the range and severity of phenotypes associated with high impact variants.

中文翻译：

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两种伪装成一种的单基因疾病：严重的先天性中性粒细胞减少症伴单核细胞增多症和非综合征性感觉神经性听力丧失。

背景我们报道了一个大家族，该家族有四个连续的世代，表现出严重的先天性中性粒细胞减少症（SCN），部分渗透性单核细胞增多和严重程度不同的听力损失的复杂表型。方法我们进行了完整的外显子组测序以鉴定致病变异。Sanger测序用于对其余家庭成员进行隔离分析。结果我们鉴定并分类了MYO6中的致病性GFI1变体和可能的致病性变体，它们共同解释了该家族中所见的复杂表型。结论我们提出了一个案例，该案例说明了广泛筛选方法的优势，该方法可用于鉴定复杂人类表型的寡聚决定簇，如果筛选仅限于有症状的靶基因组，则可能会遗漏。