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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2020

01-12-2020 | Myelodysplastic Syndrome | Research article

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

Authors: Parvathy Venugopal, Lucia Gagliardi, Cecily Forsyth, Jinghua Feng, Kerry Phillips, Milena Babic, Nicola K. Poplawski, Hugh Young Rienhoff Jr, Andreas W. Schreiber, Christopher N. Hahn, Anna L. Brown, Hamish S. Scott

Published in: BMC Medical Genetics | Issue 1/2020

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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.
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Metadata
Title
Two monogenic disorders masquerading as one: severe congenital neutropenia with monocytosis and non-syndromic sensorineural hearing loss
Authors
Parvathy Venugopal
Lucia Gagliardi
Cecily Forsyth
Jinghua Feng
Kerry Phillips
Milena Babic
Nicola K. Poplawski
Hugh Young Rienhoff Jr
Andreas W. Schreiber
Christopher N. Hahn
Anna L. Brown
Hamish S. Scott
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2020
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-020-0971-z

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