Novel pathogenic CERKL variant in Iranian familial with inherited retinal dystrophies: genotype-phenotype correlation.

Inherited retinal dystrophies (IRDs) include a large chronic heterogeneity genetic disease. While many disease-causing pathogenic variants were involved in the progression of IRD, the Ceramide Kinase Like (CERKL) gene variant in Iranian patients is not well characterized. In this study, a consanguineous Iranian family with three generations was recruited whom presented with the clinical diagnosis of autosomal recessive IRD. By targeted next-generation sequencing (TGS) and Sanger sequencing, the proband was found to have a novel, pathological homozygous deletion variant c.560_568del (p.187_190del) of the CERKL gene (NM_001030311.2) that co-segregated with the disease in all affected family members. The Cerkl is highly expressed in the later four developmental retinal stages, playing a vital role in retina degeneration. Therefore, the identification of a novel, homozygous deletion CERKL variant c.560_568del (p.187_190del) in an IRD familial cohort descent provides insights into the molecular pathogenesis of IRD and facilitates genetic counseling and disease prediction.

Novel splicing variant c. 208+2T>C in BBS5 segregates with Bardet-Biedl syndrome in an Iranian family by targeted exome sequencing.

Bardet-Biedl syndrome (BBS) is a rare genetically heterogeneous ciliopathy which accompanies retinitis pigmentosa (RP). However, the BBS5 mutation remains unclear in Iranians with BBS. The purpose of study is to evaluate genetic analyses of a BBS Iranian family using targetted exome sequencing (TES). A male 11-year-old proband and three related family members were recruited. Biochemical tests, electrocardiography and visual acuity testing, such as funduscopic, fundus photography (FP), optical coherence tomography (OCT), and standard electroretinography, were conducted. Molecular analysis and high-throughput DNA sequence analysis were performed. The proband was diagnosed with possible BBS based on the presence of three primary features and two secondary features. The TES analysis of the proband with BBS resulted in the identification of a novel, homozygous splicing variant c. 208+2T>C of the BBS5 gene (NM_152384.2) in this Iranian BBS family. This variant was confirmed and was completely co-segregated with the disease in this family by Sanger sequencing. Thus, we report a novel, homozygous splicing site variant c.208+2T>C in the BBS5 gene for the first time in the Iranian family.

Clinical and functional outcomes of vascularized bone graft in the treatment of scaphoid non-union.

INTRODUCTION: Scaphoid non-union is a challenging and complex problem. Various methods have been proposed for the management of patients with scaphoid non-union and to reduce the risk of complications. In this study, our aim was to evaluate the clinical and functional outcomes of using a vascularized bone graft in the treatment of scaphoid non-union. METHODS: Patients with scaphoid non-union who underwent 1,2 intercompartmental supraretinacular artery pedicled vascularized bone graft between January 2005 and January 2011 were enrolled. The parameters assessed included clinical and functional outcomes, radiological measures, and potential risk factors. RESULTS: Forty-one patients were finally included. Thirty patients achieved union (73%) and 11 did not. Smoking was a significant risk factor for non-union after the surgery. In patients who achieved union, grip strength and radioulnar abduction were greater in comparison to that in patients who did not achieve union. Functional measures, including the Disabilities of Arm and Shoulder score and the Modified Mayo Wrist Score, improved in patients with scaphoid union. The scaphoid length also improved significantly postoperatively in these patients. CONCLUSION: Surgical treatment of scaphoid non-union using vascularized bone graft led to a high union rate with good clinical and functional outcomes. Smoking is a risk factor for non-union, even with the use of a vascularized bone graft. Avascular necrosis was not associated with an increased risk for non-union.

Identification of a novel RPGRIP1 mutation in an Iranian family with leber congenital amaurosis by exome sequencing.

Leber congenital amaurosis (LCA) is a heterogeneous, early-onset inherited retinal dystrophy, which is associated with severe visual impairment. We aimed to determine the disease-causing variants in Iranian LCA and evaluate the clinical implications. Clinically, a possible LCA disease was found through diagnostic imaging, such as fundus photography, autofluorescence and optical coherence tomography. All affected patients showed typical eye symptoms associated with LCA including narrow arterioles, blindness, pigmentary changes and nystagmus. Target exome sequencing was performed to analyse the proband DNA. A homozygous novel c. 2889delT  (p.P963 fs) mutation in the RPGRIP1 gene was identified, which was likely the deleterious and pathogenic mutation in the proband. Structurally, this mutation lost a retinitis pigmentosa GTPase regulator (RPGR)-interacting domain at the C-terminus which most likely impaired stability in the RPGRIP1 with the distribution of polarised proteins in the cilium connecting process. Sanger sequencing showed complete co-segregation  in this pedigree. This study provides compelling evidence that the c. 2889delT  (p.P963 fs) mutation in the RPGRIP1 gene works as a pathogenic mutation that contributes to the progression of LCA.