@article {696, title = {The expanding phenotype of OFD1-related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia.}, journal = {Mol Genet Genomic Med}, volume = {7}, year = {2019}, month = {2019 Sep}, pages = {e911}, 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.

}, issn = {2324-9269}, doi = {10.1002/mgg3.911}, author = {Hannah, William B and DeBrosse, Suzanne and Kinghorn, BreAnna and Strausbaugh, Steven and Aitken, Moira L and Rosenfeld, Margaret and Wolf, Whitney E and Knowles, Michael R and Zariwala, Maimoona A} }