The expanding phenotype of OFD1-related disorders: Hemizygous loss-of-function variants in three patients with primary ciliary dyskinesia

Molecular Genetics & Genomic Medicine
William B HannahMaimoona A Zariwala

Abstract

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. 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. Some individuals with hemizygous OFD1 variants have PCD, either apparently isolated or in combination with other features of OFD1-related disorders. As clinicians consider the presence or absence of conditions allelic at OFD1, PCD should be considered part of the spectrum of OFD1-related ...Continue Reading

References

Oct 1, 1991·Journal of Medical Genetics·J GoodshipJ Burn
Aug 12, 1999·American Journal of Human Genetics·L M BrzustowiczR Weksberg
Feb 17, 2001·American Journal of Human Genetics·M I FerranteB Franco
Jun 12, 2008·Human Mutation·Clelia PrattichizzoUNKNOWN Oral-Facial-Digital Type I (OFDI) Collaborative Group
Oct 6, 2009·American Journal of Human Genetics·Karlien L M CoeneArjan P M de Brouwer
Oct 31, 2009·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Melissa A Parisi
Feb 23, 2012·European Journal of Human Genetics : EJHG·Michael FieldJozef Gecz
Oct 6, 2012·Clinical Genetics·C Thauvin-RobinetT Attié-Bitach
Jun 26, 2013·American Journal of Respiratory and Critical Care Medicine·Michael R KnowlesMargaret W Leigh
Jul 7, 2014·Nature Genetics·Christel Thauvin-RobinetMaxence V Nachury
Sep 30, 2015·Pediatric Pulmonology·Adam J ShapiroUNKNOWN Genetic Disorders of Mucociliary Clearance Consortium

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Citations

Nov 12, 2019·American Journal of Medical Genetics. Part a·Ruxandra Bachmann-GagescuDan Doherty
Sep 9, 2020·Biochemical Society Transactions·Manuela Morleo, Brunella Franco
Sep 19, 2020·Nature Reviews. Disease Primers·Julia WallmeierHeymut Omran
Nov 27, 2020·The Journal of Pediatrics·Amjad Horani, Thomas W Ferkol
Mar 28, 2021·Pharmacology & Therapeutics·Max Duong PhuMelanie Philipp
Aug 8, 2021·International Journal of Molecular Sciences·Steven K BrennanStephanie D Davis

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Methods Mentioned

BETA
Transmission
nuclear magnetic resonance
exome sequencing
electron microscopy
SGBS

Clinical Trials Mentioned

NCT02871778

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