The Expanding Phenotype of OFD1-related Disorders: Hemizygous Loss-of-function Variants in Three Patients with Primary Ciliary Dyskinesia

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2019 Aug 3

PMID 31373179

Citations 23

Authors

William B Hannah

Suzanne DeBrosse

BreAnna Kinghorn

Steven Strausbaugh

Moira L Aitken

Margaret Rosenfeld

Whitney E Wolf

Michael R Knowles

Maimoona A Zariwala

Affiliations

Soon will be listed here.

Abstract

Background: OFD1 has long been recognized as the gene implicated in the classic dysmorphology syndrome, oral-facial-digital syndrome type I (OFDSI). Over time, pathogenic variants in OFD1 were found to be associated with X-linked intellectual disability, Joubert syndrome type 10 (JBTS10), Simpson-Golabi-Behmel syndrome type 2 (SGBS2), and retinitis pigmentosa. Recently, OFD1 pathogenic variants have been implicated in primary ciliary dyskinesia (PCD), a disorder of the motile cilia with a phenotype that includes recurrent oto-sino-pulmonary infections, situs abnormalities, and decreased fertility.

Methods: We describe three male patients with PCD who were found to have hemizygous pathogenic variants in OFD1, further supporting that PCD is part of a clinical spectrum of OFD1-related disorders. In addition, we provide a review of the available clinical literature describing patients with OFD1 variants and highlight the phenotypic variability of OFD1-related disease.

Results: Some individuals with hemizygous OFD1 variants have PCD, either apparently isolated or in combination with other features of OFD1-related disorders.

Conclusion: As clinicians consider the presence or absence of conditions allelic at OFD1, PCD should be considered part of the spectrum of OFD1-related disorders. Understanding the OFD1-related disease spectrum may allow for more focused genetic testing and more timely management of treatable sequelae.

Citing Articles

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Two Pediatric Cases of Primary Ciliary Dyskinesia Caused by Loss-of-Function Variants in Oral-Facial-Digital Syndrome Gene, .

Xu Y, Tsurinaga Y, Matsumoto T, Muta R, Yano T, Sakaida H Case Rep Genet. 2024; 2024:1595717.

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