BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population. METHODS: Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing. RESULTS: Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable. CONCLUSION: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.
Crossing Over, Genetic ; Diagnosis ; Haplotypes ; Humans ; Mass Screening ; Microsatellite Repeats ; Pedigree ; Polycystic Kidney, Autosomal Dominant* ; Population Characteristics ; Recombination, Genetic

PURPOSE: This study aimed to investigate the possible association between psychological disorders and risky driving behavior (RDB) in Iran. METHODS: This case-control study conducted in Shiraz, Iran in 2021. The case group included drivers with psychological disorders and the control group included those without any disorders. The inclusion criteria for selecting patients were: active driving at the time of the study, being 18 - 65 years old, having a driving license, having a psychological disorder including depression, bipolar disorder, anxiety spectrum disorder, or psychotic disorder spectrum confirmed by a psychiatrist, and completing an informed consent form. The exclusion criterion was the existence of conditions that interfered with answering and understanding the questions. The inclusion criteria for selecting the healthy cases were: active driving at the time of the study, being 18 - 65 years old, having a driving license, lack of any past or present history of psychiatric problems, and completing an informed consent form. The data were gathered using a researcher-made checklist and Manchester driving behavior questionnaire. First, partition around medoids method was used to extract clusters of RDB. Then, backward logistic regression was applied to investigate the association between the independent variables and the clusters of RDB. RESULTS: The sample comprised of 344 (153 with psychological disorder and 191 without confirmed psychological disorder) drivers. Backward elimination logistic regression on total data revealed that share of medical expenditure ≤ 10% of total household expenditure (OR = 3.27, 95% CI: 1.48 - 7.24), psychological disorder (OR = 3.08, 95% CI: 1.67 - 5.70), and substance abuse class (OR = 6.38, 95% CI: 3.55 - 11.48) were associated with high level of RDB. CONCLUSION Substance abuse, psychological illnesses, and share of medical costs from total household expenditure were found to be main predictors of RDB. Further investigations are necessary to explain the impact of different psychological illnesses on driving behavior.
Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Automobile Driving ; Iran ; Case-Control Studies ; Mental Disorders/epidemiology* ; Surveys and Questionnaires ; Risk-Taking