Clinical AreaPsychiatry

Here you will find the disease-related gene panels available for the clinical area specified above.

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Molecular genetic diagnostics are used to clarify the hereditary causes of thousands of genetically determined diseases. Congenital malformations of the nervous system often appear sporadically - is there a genetic (co-)cause? Many inherited psychiatric disorders are demonstrably based on genetic changes and lead to disorders in the proteins that build up the central nervous system. DNA diagnostics therefore often involves a step-by-step procedure in which the most frequent mutations are first tested before the very rare genetic causes are also identified in parallel approaches using extensive and cost-intensive panel procedures. Mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis using the Sanger technique.

The inheritance patterns of genetically caused diseases are the basis of genetic counselling for patients, persons at risk and affected families. Over the past 30 years, thousands of genes that cause hereditary diseases or contribute to the development of genetic disorders have been successively characterised. Current results of genetic research have a direct impact on the diagnostic procedure in the laboratory and in genetic counselling. For example, mutations in independent genes on different chromosomes can cause clinically indistinguishable syndromes (genetic heterogeneity in dementia or psychomotor retardation). On the other hand, different mutations in one and the same gene lead to clinically clearly separated disease entities (FMR1 gene: intellectual impairment or Fragile X-Tremor Ataxia Syndrome [FXTAS] or premature ovarian failure).

Formal genetically and etiologically, the following groups of genetic diseases can be distinguished:

• monogenic diseases (autosomal or X-chromosomal inheritance)
• mitochondrial diseases (maternal or autosomal inheritance)
• multifactorial diseases (interaction of several to many genes plus environmental factors) DNA diagnostics therefore often involves a step-by-step procedure in which the most frequently observed mutations are first tested before the very rare genetic causes are also identified in parallel approaches using expanded and cost-intensive panel procedures. Any mutations found or all variants with unclear significance (VUS) are verified by DNA sequence analysis Sanger technology.

A technically less complex DNA diagnosis is possible if Huntington disease is suspected or predicted, and the mutation is always uniform: A certain repetitive region of the Huntingtin (HTT) gene is expanded beyond a critical sequence length, much like in about three dozen other model diseases, which are mainly characterized by neurological-psychiatric symptoms (e.g. spinocerebellar ataxias [SCAs] with sometimes also predominantly psychiatric symptoms).

The DNA-diagnostic situation is completely different in the case of dementia diseases. First, psychiatric differentiation should be made between: Alzheimer dementia (AD), vascular or frontotemporal dementia (FTD), Parkinson disease dementia and Lewy-Body dementia The proportion of familial Alzheimer disease (FAD) in dementia patients is less than 5%. In FAD, various mutations have been described in three genes: Amyloid precursor protein (APP), presenilin 1 (PS1) and 2 (PS2). In FTD, mutations in five genes are known to explain the majority of autosomal dominant cases in this category: Microtubule-associated protein tau (MAPT), progranulin (PGN), valosin-containing protein (VCP), charged multi-vesicular body protein 2B (CHMP2B) and chromosome 9 open reading frame 72 (C9ORF72) gene. The latter is probably the most frequently associated gene with hereditary FTD and with hereditary FTD amyotrophic lateral sclerosis. The S3 guideline "Dementia" does not recommend an isolated determination of the apolipoprotein E genotype as a genetic risk factor due to a lack of diagnostic selectivity and low predictive value.

The comparatively common psychiatric conditions depression (formerly endogenous depression) and schizophrenia cannot be addressed with direct DNA diagnostics. Although hereditary relations appear obvious, they can only be proven experimentally at great expense. Many processes in the brain are involved in depression and schizophrenia, but the contributions of individual variant genes are very small. The suspected regions in the genome are lost in the background noise of genetic differences unless samples from hundreds of thousands of well-characterised patients and healthy control persons are used.