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

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.

journal_name

BMC Med Genet

journal_title

BMC medical genetics

authors

Venugopal P,Gagliardi L,Forsyth C,Feng J,Phillips K,Babic M,Poplawski NK,Rienhoff HY Jr,Schreiber AW,Hahn CN,Brown AL,Scott HS

doi

10.1186/s12881-020-0971-z

subject

Has Abstract

pub_date

2020-02-17 00:00:00

pages

35

issue

1

issn

1471-2350

pii

10.1186/s12881-020-0971-z

journal_volume

21

pub_type

杂志文章

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