|Title||The expanding phenotype of OFD1-related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Hannah, WB, DeBrosse, S, Kinghorn, BA, Strausbaugh, S, Aitken, ML, Rosenfeld, M, Wolf, WE, Knowles, MR, Zariwala, MA|
|Journal||Mol Genet Genomic Med|
|Date Published||2019 Sep|
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.
|Alternate Journal||Mol Genet Genomic Med|
|PubMed Central ID||PMC6732318|
|Grant List||5R01HL071798-10 / HL / NHLBI NIH HHS / United States |
R01 HL071798 / HL / NHLBI NIH HHS / United States
UM1 HG006504 / HG / NHGRI NIH HHS / United States
U54 HL096458 / HL / NHLBI NIH HHS / United States
5U54HL096458-11 / HL / NHLBI NIH HHS / United States