Two monogenic disorders masquerading as one: severe congenital neutropenia with monocytosis and non-syndromic sensorineural hearing loss

• Main Authors: Parvathy Venugopal, Lucia Gagliardi, Cecily Forsyth, Jinghua Feng, Kerry Phillips, Milena Babic, Nicola K. Poplawski, Hugh Young Rienhoff, Andreas W. Schreiber, Christopher N. Hahn, Anna L. Brown, Hamish S. Scott
• Format: Article
• Language: English
• Published: BMC 2020-02-01
• Series: BMC Medical Genetics
• Subjects: Neutropenia; Congenital neutropenia; Leukemia predisposition; Polygenic inheritance; Hearing loss
• Online Access: http://link.springer.com/article/10.1186/s12881-020-0971-z

Abstract 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.