A novel mutation and variable phenotypic expression in a large consanguineous pedigree with Jalili syndrome.

PurposeJalili syndrome is an autosomal recessive disorder characterized by simultaneous appearance of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI). Mutations in CNNM4 gene have been identified as the underlying cause of the syndrome. In this study, we investigated a large affected family to identify the causative mutation.Patients and MethodsA seven-generation family with 24 members affected with Jalili syndrome were enrolled in the study. Comprehensive ophthalmologic and dental examinations were performed on them. The entire coding region of CNNM4 gene was sequenced for detection of potential mutations.ResultsOcular examinations showed nystagmus and photophobia along with early onset visual impairment. Fundoscopic exams revealed a spectrum of macular dystrophies in different family members, from macular coloboma and advanced form of beaten bronze macular dystrophy (bull's eye) to milder form of macular thinning along with a range of pigmentary changes and vascular attenuation in the posterior pole and periphery. Scotopic and photopic electro-retinographic responses (ERGs) were extinguished or significantly depressed. Mutation analysis revealed a novel mutation (c.1091delG) in homozygous form in the patients and as a heterozygous form in the normal carrier subjects.ConclusionWe identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome.

Rare chromosome structural aberration characterizing oncology malignancy.

UNLABELLED: Ring chromosome aberration are rare abnormality potentially involving any chromosome in patients diagnosing in Oncology. The present review and case study has focused on the ring chromosome associated with oncology malignancies. MATERIAL AND METHODS: An electronic peer review article search was performed systematically to obtain relevant literature with the CINAHL, Google scholar, and Pub Med databases. The keywords included marker, abnormalities, structural, Ring chromosome. The inclusion criteria for the review were that the documents were original quantitative research and published in English. This was also initiated using Medline, Mitelman database (http://cgap.nci.nih.gov/Chromosomes/Mitelman), Danish cytogenetic register and other pertinent web references on ring chromosomes in Oncology malignancies. Articles that were not directly relevant to the present objective were excluded. Also the un-stimulated bone marrow specimen of present case manipulated with Methotrexate cells culture synchronization and finally was treated by GTGbanding technique. RESULTS: Ring chromosome was observed in 10% of the total cells. Cytogenetic analysis demonstrated apparently ring (15) 46, XY, r(15) karyotype. The clinical findings revealed history of nausea, loss of appetite, diarrhea, night sweats, and a weight loss, anemia and diagnosed as accelerated CML. CONCLUSION: Our finding adds to the spectrum of both morphology and genetic rearrangements in oncology malignancies. Additional future analyses in similar subject will be necessary to draw firm conclusions.

Dominant and Protective Role of the CYTH4 Primate-Specific GTTT-Repeat Longer Alleles Against Neurodegeneration.

Primate-specific genes and regulatory mechanisms could provide insight into human brain functioning and disease. In a genome-scale analysis of the entire protein-coding genes listed in the GeneCards database, we have recently reported human genes that contain "exceptionally long" short tandem repeats (STRs) in their core promoter, which may be of adaptive/selective evolutionary advantage in this species. The longest tetra-nucleotide repeat identified in a human gene core promoter belongs to the CYTH4 gene. This GTTT-repeat is specific to Hominidae and Old World monkeys, and the shortest allele of this repeat, (GTTT)6, is linked with neural dysfunction and type I bipolar disorder in human. In the present study, we sought a possibly broader role for the CYTH4 gene core promoter GTTT-repeat in neural functioning and investigated its allelic distribution in a total of 949 human subjects, consisting of two neurodegenerative disorders, multiple sclerosis (MS) (n = 272) and Alzheimer's disease (AD) (n = 257), and controls (n = 420). The range of the alleles of this GTTT-repeat in the human sample studied was between 6- and 9-repeats. The shortest allele, (GTTT)6, was significantly in excess in the MS and AD patients in comparison with the controls (p < 0.004). The 6/6, 6/7, and 7/7 genotypes were in excess in the MS and AD patients, whereas the overall frequency of all other genotypes (consisting of at least one longer allele, i.e., 8- or 9-repeat) was higher in the controls (p < 0.005), indicating a dominant and protective effect for the longer alleles against neurodegeneration. This is the first indication of the involvement of a primate-specific STR in neurodegeneration in humans. We propose an adaptive evolutionary role for the expansion of the CYTH4 gene core promoter GTTT-repeat in the human brain, which is supported by a link between the shortest allele of this repeat with neuropsychiatric disorders.

HLA-DRA is associated with Parkinson's disease in Iranian population.

The rs3129882, a noncoding variant in HLA-DR, was found to be associated with Parkinson's disease (PD) using several genome-wide association studies. The aim of this replication study was to explore the relationship between this variant and PD in Iranian population. Genomic DNA was extracted from peripheral blood samples, and the rs3129882 SNP was genotyped using a PCR-RFLP method in 520 PD patients and 520 healthy Iranian controls. Significant differences were found in allele frequencies between patients and controls (χ(2) = 4.64, P = 0.031). Under additive and dominant models, the association of the SNP with PD risk is significant, where the A allele was observed to be protective. The results suggest that rs3129882 polymorphism may be a risk factor for PD in Iranian. This is the first study reporting such an association in this population. More replication studies are needed to confirm this data.

Hepatitis B virus infection in patients with blood disorders: a concise review in pediatric study.

Childhood Hepatitis B virus (HBV) infection causes both medical and public health challenges. Infants who acquire HBV parentally have up to 90% risk of developing chronic HBV infection. It is now estimated that approximately 10% of worldwide cancers are attributable to viral infection, with the vast majority (>85 %) occurring in the developing world. In this distribution, elevated rate and prevalence of HBV marker have been found in patients with malignancies as compared to the general population. By reviewing the web-based search for all Persian and English types of scientific peer review published articles initiated using Iran Medex, MEDLINE/PubMed, CINAHL and other pertinent references on websites about HBV and HCV blood disorders. The high prevalence of HBV and HCV infective markers was detected in patients with different malignancies. Moreover, identification of high prevalence of HBV infective markers in leukemia patients proposed strong association between hepatitis viral infections and leukemia.