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An spanish study of secondary findings in families affected with mendelian disorders: choices, prevalence and family history.

ABSTRACT: Clinical exome sequencing has the potential to identify pathogenic variants unrelated to the purpose of the study (secondary findings, SFs). Data describing actual choices of SFs in participants in a clinical setting and factors influencing their decision are virtually non-existant in Europe. In this work, we report the acceptance rate of SFs, calculate their prevalence and study factors associated with the decision in a cohort of patients affected with a rare genetic disorder in a Spanish Hospital. Finally, we re-examine the presence of previously non reported family history in positive cases. We retrospectively reviewed informed consent choices and SF results from 824 unrelated probands affected with rare genetic disorders who underwent whole-genome or exome sequencing. Ninety percent of families (740/824) affected with rare disorders wished to be informed of SFs. Declining SFs was associated with a prenatal setting (30% vs. 8.7%, p = 0.025), consanguinity (19% vs. 8.7%, p = 0.013), male gender (10.6% vs. 1.5%, p = 0.00865) and the proband being a minor (10.6% vs. 1.5%, p = 0.014). Overall, 27 pathogenic or likely pathogenic variants were identified in 27 individuals, with an SF prevalence of 3.6%. Disclosure of SFs increased the percentage of positive family histories and resulted in early diagnosis or changes in the management of 10 individuals from five families. We show that the acceptance of SFs in Spain is high and the disclosure of SFs leads to a clinically meaningful change in the medical management of individuals.

SUBMITTER: Codina-Sola M

PROVIDER: S-EPMC9905470 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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An spanish study of secondary findings in families affected with mendelian disorders: choices, prevalence and family history.

Codina-Solà Marta M Trujillano Laura L Abulí Anna A Rovira-Moreno Eulàlia E Muñoz-Cabello Patricia P Campos Berta B Fernández-Álvarez Paula P Palau Dolors D Carrasco Estela E Valenzuela Irene I Cueto-González Anna Maria AM Lasa-Aranzasti Amaia A Limeres Javier J Leno-Colorado Jordi J Costa-Roger Mar M Moles-Fernández Alejandro A Balmaña Judith J Díez Orland O Cuscó Ivon I Garcia-Arumí Elena E Tizzano Eduardo Fidel EF

European journal of human genetics : EJHG 20221129 2

Clinical exome sequencing has the potential to identify pathogenic variants unrelated to the purpose of the study (secondary findings, SFs). Data describing actual choices of SFs in participants in a clinical setting and factors influencing their decision are virtually non-existant in Europe. In this work, we report the acceptance rate of SFs, calculate their prevalence and study factors associated with the decision in a cohort of patients affected with a rare genetic disorder in a Spanish Hospi ...[more]

PMID: 36446894

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Project description:BackgroundPsychiatric disorders are characterized by alteration in emotions, mood and behavior. Genetics is known to play a significant role in the development of psychiatric disorders. Genome-wide association studies have identified several loci associated with psychiatric illnesses. We hypothesize the existence of rare variants following Mendelian recessive mode of inheritance. These variants can be identified in families with multiple affected individuals born to unaffected consanguineous parents.MethodsWe visited psychiatric outpatient departments of multiple hospitals in Lahore, Pakistan. We focused on psychosis, as it can occur in several DSM disorders such as schizophrenia, dementia and bipolar disorder. After clinical diagnosis by an American trained psychiatrist, detailed clinical assessments using Diagnostic Interview for Genetic Studies (DIGS), Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD), Positive and Negative Syndrome Scale (PANSS), Hamilton Depression and Anxiety Rating Scale (HAM-D; HAM-A) were administered to all willing affected and unaffected participants.ResultsWe identified eight pedigrees with two or more psychotic individuals in each family. Clinical diagnoses determined by their psychiatrists included ten individuals with schizophrenia; four individuals with psychosis and bipolar disorder; and two patients with "unspecified psychosis." The rating instruments rigorously confirmed the diagnosis of psychosis in the affected patients from the six families as well as the absence of psychotic disorders in unaffected individuals from the six families. We obtained DNA samples from willing members of all eight families for future genetic analyses.ConclusionOur research highlights an alternative approach to discovery of rare recessively inherited genetic variants causing psychiatric disorders that have remained unidentified to date. These findings could illuminate underlying biological mechanisms leading toward development of targeted therapies in future.

Dataset Information

An spanish study of secondary findings in families affected with mendelian disorders: choices, prevalence and family history.

Publications

An spanish study of secondary findings in families affected with mendelian disorders: choices, prevalence and family history.

Similar Datasets

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