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Background: Pathogenic variants in the CEP78 gene can present as atypical Usher syndrome or as retinitis pigmentosa. Here, we present a review of all reported cases of CEP78 variants in the literature to date and present a novel variant of CEP78, c.1261_1262delinsA, in a consanguineous northern Finnish family with two individuals. Materials and methods: Our patients were first discovered in a registry-based study. Later, they gave their written consent for this study. In order to describe the genotype and phenotype, their historic clinical patient data and genetic data were gathered, and a clinical ophthalmic examination and an audiogram were performed. For this review, a PubMed search using the keyword CEP78 was carried out. The first article on CEP78 was published in the year 2007, and the publications from the years 2007–2021 were included. Results: A large gene panel identified a homozygous CEP78 c.1261_1262delinsA variant in two affected siblings. In addition to the classical signs of retinitis pigmentosa, both siblings had large round atrophic spots in the mid periphery, and hyperautofluorescence of the macula. Patient 1 had age-related hearing impairment; patient 2 had normal hearing. In total, 20 articles have been published about CEP78. Eight of these papers report patient data with the affected individuals typically having retinal dystrophy combined with sensorineural hearing impairment, classified as atypical Usher syndrome. Conclusions: Here, we present a comprehensive review of CEP78 and expand the knowledge of pathogenic CEP78 variants and the phenotypic variety.

Aim: To perform genealogical and clinical studies in Finnish families with X linked ocular albinism (OA1), including characterisation of the potential misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs), and to determine the mutation behind the disease. Methods: Three families with OA1 were clinically examined. VEFs were measured in two affected males and in one female carrier to characterise the cortical activation pattern after monocular visual stimulation. The neuronal sources of the VEFs were modelled with equivalent current dipoles (ECDs) in a spherical head model. All coding exons of the OA1 gene were screened for mutations by single strand conformation analysis and direct polymerase chain reaction sequencing. Results: Genealogical studies revealed that the three families were all related. The affected males had foveal hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable nystagmus, iris transillumination, and hypopigmentation of the retinal pigment epithelium. The ECD locations corresponding to the VEFs revealed abnormal crossing of the optic fibres in both affected males, but not in the carrier female. A novel point mutation, leading to a STOP codon, was identified in the fifth exon of the OA1 gene. Conclusions: The data indicate that the novel mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the family studied. VEFs with ECD analysis was successfully used to demonstrate abnormal crossing of the optic fibres.

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

OBJECTIVE: A recent study showed a higher frequency of GA deletion at rs67491583 in African American colorectal cancer (CRC) patients compared to controls, suggesting a likely contribution of this allele to racial disparity in CRC risk predisposition. We conducted a pilot study in an indigenous African population to evaluate this potential CRC risk variant. METHODS: We collected epidemiological data and biological specimen from consenting consecutive CRC cases and controls presenting at the Oncology Clinic of University College Hospital, Ibadan from 2001 to 2007. We examined germline DNA for delGA by PCR-amplification of two overlapping fragments using standard primers. The products were directly sequenced using Applied Biosystems BigDye v3.1 sequencing chemistry and AB13730 automatic DNA sequencer. RESULTS: There were 45 cases and 45 controls of which genotyping was successful in 39 cases and 38 controls. There were 5 heterozygous and 2 homozygous GA deletions with frequency of 11.54% (9/78) among cases whereas there were 8 heterozygous and 1homozygous GA deletions among controls with frequency of 13.15% (10/76). (p= 0.79, OR 0.88, 95% CI 0.34-2.28) CONCLUSION: This study suggests that there is no association between the delGA (rs67491583) variant and CRC risk in this indigenous African population. However our sample size was small and the participants were not ethnically homogenous. Further studies are required to evaluate this marker in African CRC.