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Schizophrenia is a heritable neurocognitive disorder affecting about 1% of the population, and usually has an onset age at around 21-25 in males and 25-30 in females. Recent advances in genetics have helped to identify many common and rare variants for the liability to schizophrenia. Earlier evidence appeared to suggest that younger onset age is associated with higher genetic liability to schizophrenia. Clinical longitudinal research also found that early and very-early onset schizophrenia are associated with poor clinical, neurocognitive, and functional profiles. A recent study reported a heritability of 0.33 for schizophrenia onset age, but the genetic basis of this trait in schizophrenia remains elusive. In the preGenome-Wide Association Study (GWAS) era, genetic loci found to be associated with onset age were seldom replicated. In the post-Genome-Wide Association Study era, new conceptual frameworks are needed to clarify the role of onset age in genetic research in schizophrenia, and to identify its genetic basis. In this review, we first discussed the potential of onset age as a characterizing/subtyping feature for psychosis, and as an important phenotypic dimension of schizophrenia. Second, we reviewed the methods, samples, findings and limitations of previous genetic research on onset age in schizophrenia. Third, we discussed a potential conceptual framework for studying the genetic basis of onset age, as well as the concepts of susceptibility, modifier, and "mixed" genes. Fourth, we discussed the limitations of this review. Lastly, we discussed the potential clinical implications for genetic research of onset age of schizophrenia, and how future research can unveil the potential mechanisms for this trait. [ABSTRACT FROM AUTHOR]

Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals.

Von Hippel–Lindau (VHL) disease is a rare autosomal-dominant inherited tumor syndrome. We aimed to analyze the correlations between frequent VHL mutations and phenotypes in Chinese VHL families. We screened 540 patients from 187 unrelated Chinese VHL families for 19 frequent VHL mutations. The penetrance and mean age at onset for VHL-associated susceptible organs were calculated and compared. The overall survival of VHL patients was described with Kaplan–Meier curves. Among the 19 frequent germline mutations, there were four hotspot mutation sites (194, 481, 499, and 500). Missense mutations were the most common types of mutations (70.0%) followed by nonsense mutations (20.0%) and splicing mutations (10.0%). Due to the diversity of these mutations, the penetrance for each organ and the age at onset are distinct. Even in cases of similar mutations, variance in the penetrance and age at onset was observed. The mean age at death for the patients in this cohort was 42.4 ± 13.5 years, and variability was observed in the Kaplan–Meier curves. We present a precise summary of the phenotypes for the frequent VHL mutations in the largest Chinese VHL cohort, which provides valuable strategies for genetic counseling and clinical surveillance of VHL individuals. [ABSTRACT FROM AUTHOR]

Schizophrenia is a heritable neurocognitive disorder affecting about 1% of the population, and usually has an onset age at around 21-25 in males and 25-30 in females. Recent advances in genetics have helped to identify many common and rare variants for the liability to schizophrenia. Earlier evidence appeared to suggest that younger onset age is associated with higher genetic liability to schizophrenia. Clinical longitudinal research also found that early and very-early onset schizophrenia are associated with poor clinical, neurocognitive, and functional profiles. A recent study reported a heritability of 0.33 for schizophrenia onset age, but the genetic basis of this trait in schizophrenia remains elusive. In the pre-Genome-Wide Association Study (GWAS) era, genetic loci found to be associated with onset age were seldom replicated. In the post-Genome-Wide Association Study era, new conceptual frameworks are needed to clarify the role of onset age in genetic research in schizophrenia, and to identify its genetic basis. In this review, we first discussed the potential of onset age as a characterizing/subtyping feature for psychosis, and as an important phenotypic dimension of schizophrenia. Second, we reviewed the methods, samples, findings and limitations of previous genetic research on onset age in schizophrenia. Third, we discussed a potential conceptual framework for studying the genetic basis of onset age, as well as the concepts of susceptibility, modifier, and "mixed" genes. Fourth, we discussed the limitations of this review. Lastly, we discussed the potential clinical implications for genetic research of onset age of schizophrenia, and how future research can unveil the potential mechanisms for this trait., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhan, Sham, So and Lui.)