Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene are the most common single cause of retinitis pigmentosa, accounting for up to 15 to 20% of cases in Caucasians. A total of 240 different RPGR mutations have been reported, including 24 novel ones in this work, which are associated with X-linked retinitis pigmentosa (XLRP) (95%), cone, cone-rod dystrophy, or atrophic macular atrophy (3%), and syndromal retinal dystrophies with ciliary dyskinesia and hearing loss (2%). All disease-causing mutations occur in one or more RPGR isoforms containing the carboxyl-terminal exon open reading frame 15 (ORF15), which are widely expressed but show their highest expression in the connecting cilia of rod and cone photoreceptors. Of reported RPGR mutations, 55% occur in a glutamic acid-rich domain within exon ORF15, which accounts for only 31% of the protein. RPGR forms complexes with a variety of other proteins and appears to have a role in microtubular organization and transport between photoreceptor inner and outer segments.
Summary
Protein Z‐dependent protease inhibitor (ZPI) is a serpin that inhibits the activated coagulation factors X and XI. The precise physiological significance of ZPI in the control of haemostasis is unknown although a deficiency of ZPI may be predicted to alter this balance. The coding region of the ZPI gene was screened for mutations using denaturing high‐performance liquid chromatography. 16 mutations/polymorphisms within the coding region of ZPI were identified including two mutations, which generated stop codons at residues R67 and W303. We observed nonsense mutations within the ZPI gene in 4·4% of thrombosis patients (n = 250) compared with 0·8% of controls (n = 250). The difference in distribution of stop codon mutations between thrombosis patients and controls was significant (P = 0·02) with an odds ratio of 5·7 (95% confidence interval, 1·25–26·0). Our results suggest an association between ZPI deficiency and venous thrombosis and we propose that ZPI deficiency is potentially a new form of thrombophilia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.