DYNC2H1 hypomorphic or retina-predominant variants cause nonsyndromic retinal degeneration

Purpose: Determining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD). Methods: Genome and exome sequencing were performed for five unrelated cases of IRD with no identified variant. In vitro assays were developed to validate the variants identified (fibroblast assay, induced pluripotent stem cell [iPSC] derived retinal organoids, and a dynein motility assay). Results: Four novel DYNC2H1 variants (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) and one previously reported variant (V5, g.103339363T>G) were identified. In proband 1 (V1/V2), V1 was predicted to introduce a premature termination codon (PTC), whereas V2 disrupted the exon 41 splice donor site causing incomplete skipping of exon 41. V1 and V2 impaired dynein-2 motility in vitro and perturbed IFT88 distribution within cilia. V3, homozygous in probands 2–4, is predicted to cause a PTC in a retina-predominant transcript. Analysis of retinal organoids showed that this new transcript expression increased with organoid differentiation. V4, a novel missense variant, was in trans with V5, previously associated with Jeune asphyxiating thoracic dystrophy (JATD). Conclusion: The DYNC2H1 variants discussed herein were either hypomorphic or affecting a retina-predominant transcript and caused nonsyndromic IRD. Dynein variants, specifically DYNC2H1 variants are reported as a cause of non syndromic IRD

Painful hip arthroplasty: definition.

Total hip arthroplasty (THA) has been indicated as the surgical intervention with greatest improvement in pain and physical function. However some patients continue to experience hip pain after elective surgery. We investigate prognostic factors that negatively affect treatment effectiveness and the patient outcome. The "hip region" constitutes the groin, buttock, upper lateral thigh, greater trochanteric area, and the iliac crest. Pain originating from various sources and not directly linked to prosthesis may be perceived here and includes the lumbosacral spine, referred pain from abdominal organs and soft tissue sources such as trochanteric bursitis, tendinitis, hip abductor dysfunction, and inguinal hernia. An accurate assessment of the pain cause is extremely difficult to construct and a complete differential diagnosis is fundamental. We assess all the possible causes of hip pain after THA and we divide them depending on the presence or absence of radiographic signs

WHICH PHYSICAL ENTITIES OF ENVIRONMENTAL VISUAL STIMULI CAUSE EEG DISCHARGES IN PHOTOSENSITIVE EPILEPSY PATIENTS? A PILOT STUDY WITH AMBULATORY EEG AND ARTIFICIAL EYE

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