Duane retraction syndrome: Type II with severe abducens nerve hypoplasia on magnetic resonance imaging.

Duane retraction syndrome is a congenital oculomotor disorder characterized by horizontal eye movement limitations with palpebral fissure narrowing and globe retraction on attempted adduction. Recent reports showed the absence of the subarachnoid part of the abducens nerve on magnetic resonance imaging (MRI) in types I and III. We present a case of Duane syndrome type II, in which severe hypoplasia of the abducens nerve was revealed on high-resolution MRI

Duane retraction syndrome: Type II with severe abducens nerve hypoplasia on magnetic resonance imaging.

Duane retraction syndrome is a congenital oculomotor disorder characterized by horizontal eye movement limitations with palpebral fissure narrowing and globe retraction on attempted adduction. Recent reports showed the absence of the subarachnoid part of the abducens nerve on magnetic resonance imaging (MRI) in types I and III. We present a case of Duane syndrome type II, in which severe hypoplasia of the abducens nerve was revealed on high-resolution MRI

Duane retraction syndrome: MRI features in two cases.

PURPOSE: Neuroimaging findings in Duane's retraction syndrome (DRS), through magnetic resonance imaging (MRI), suggest that aplasia of the abducens nerve (VI) can be responsible for several forms of DRS. METHODS: Brain MRI was performed in two children of 2.5 and 7 years of age with left sided DRS type II and right sided DRS type I, respectively. 3D T2 weighted images through the brainstem were acquired in order to visualize the cranial nerves especially the abducens (VI) and oculomotor (III) nerves. RESULTS: The abducens nerve on the affected side could not be observed in these two different types of DRS with normal morphology of the third nerves. CONCLUSION: Absence of the VI nerve has been described recently in DRS types I and III only, while DRS type II is usually associated with normal VI nerve on MRI. However our results show that aplasia of the VI nerve can also be seen in DRS type II resulting in new insight of the pathogenesis of this clinical entity

Duane retraction syndrome: MRI features in two cases.

PURPOSE: Neuroimaging findings in Duane's retraction syndrome (DRS), through magnetic resonance imaging (MRI), suggest that aplasia of the abducens nerve (VI) can be responsible for several forms of DRS. METHODS: Brain MRI was performed in two children of 2.5 and 7 years of age with left sided DRS type II and right sided DRS type I, respectively. 3D T2 weighted images through the brainstem were acquired in order to visualize the cranial nerves especially the abducens (VI) and oculomotor (III) nerves. RESULTS: The abducens nerve on the affected side could not be observed in these two different types of DRS with normal morphology of the third nerves. CONCLUSION: Absence of the VI nerve has been described recently in DRS types I and III only, while DRS type II is usually associated with normal VI nerve on MRI. However our results show that aplasia of the VI nerve can also be seen in DRS type II resulting in new insight of the pathogenesis of this clinical entity

Codon-optimized RPGR improves stability and efficacy of AAV8 gene therapy in two mouse models of X-linked retinitis pigmentosa

X-linked retinitis pigmentosa (XLRP) is generally a severe form of retinitis pigmentosa, a neurodegenerative, blinding disorder of the retina. 70% of XLRP cases are due to mutations in the&nbsp;retina-specific isoform of the gene encoding retinitis pigmentosa GTPase regulator (RPGRORF15). Despite successful&nbsp;RPGRORF15&nbsp;gene replacement with adeno-associated viral (AAV) vectors being established in a number of animal models of XLRP, progression to human trials has not yet been possible. The inherent sequence instability in the purine-rich region of&nbsp;RPGRORF15&nbsp;(which contains highly repetitive nucleotide sequences) leads to unpredictable recombination errors during viral vector cloning. While deleted RPGR may show some efficacy in animal models, which have milder disease, the therapeutic effect of a mutated RPGR variant in patients with XLRP cannot be predicted. Here, we describe an optimized gene replacement therapy for human XLRP disease using an AAV8 vector that reliably and consistently produces the full-length correct RPGR protein. The glutamylation pattern in the RPGR protein derived from the codon-optimized sequence is indistinguishable from the wild-type variant, implying that codon optimization does not significantly alter post-translational modification. The codon-optimized sequence has superior stability and expression levels in&nbsp;vitro. Significantly, when delivered by AAV8 vector and driven by the rhodopsin kinase promoter, the codon-optimized RPGR rescues the disease phenotype in two relevant animal models (Rpgr&minus;/y&nbsp;and&nbsp;C57BL/6JRd9/Boc) and shows good safety in&nbsp;C57BL6/J&nbsp;wild-type mice. This work provides the basis for clinical trial development to treat patients with XLRP caused by RPGR mutations.</p