Blended Phenotypes in Individuals With Rare Diseases: A Brazilian Case Series

The growing use of whole exome sequencing and whole genome sequencing in clinical practice has revealed the existence of a group of individuals that do not fit into only one molecular diagnosis. These subjects are those in whom pathogenic or likely pathogenic variants occur in more than one gene, creating "blended phenotypes" There are also genes that warrant reporting, even if they are not associated with the primary phenotype, referred to as 'secondary findings'. In this report, we analyze the prevalence of blended phenotypes in a cohort of 447 individuals who underwent broad genomic sequencing and also present a case series of eight probands who presented multiple diagnoses, generating a mixed phenotype and creating a peculiar clinical situation. In total, 3.86% (8/207) were found to have blended phenotypes, which would have been missed had those individuals not undergone comprehensive genetic testing. We reflect upon the clinical complexity of such cases and explore the consequences of the use of broad sequencing strategies in clinical practice, particularly focusing on the potential to provide a more complete diagnostic scenario. By acknowledging and understanding the complexities of blended phenotypes, clinicians can adopt a more nuanced and tailored approach to patient care.

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Publication Details

Journal
American Journal of Medical Genetics Part A
Published
2025-08-05
DOI
https://doi.org/10.1002/ajmg.a.64209
Primary Topic
Genomics and Rare Diseases
Type
article
Field-Weighted Citation Impact
0.00

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article

Blended Phenotypes in Individuals With Rare Diseases: A Brazilian Case Series

Bianca Domit Werner Linnenkamp, Noriko Miyake, Bruno de Oliveira Stephan, Yuta Inoue et al.
1 links
American Journal of Medical Genetics Part A
Genomics and Rare Diseases
article

Blended Phenotypes in Individuals With Rare Diseases: A Brazilian Case Series

Bianca Domit Werner Linnenkamp, Noriko Miyake, Bruno de Oliveira Stephan, Yuta Inoue, Ken Saida, Débora Romeo Bertola, Rachel Sayuri Honjo, Caroline Brandão Piai, Naomi Tsuchida, Masamune Sakamoto, Naomichi Matsumoto, Isabela Dorneles Pasa, Chong Ae Kim, F P Valente, Marcella Cardoso Allegro, Priscila Barbosa Betty, Gabriela Yumi Goto Salti
article en

Abstract

The growing use of whole exome sequencing and whole genome sequencing in clinical practice has revealed the existence of a group of individuals that do not fit into only one molecular diagnosis. These subjects are those in whom pathogenic or likely pathogenic variants occur in more than one gene, creating "blended phenotypes" There are also genes that warrant reporting, even if they are not associated with the primary phenotype, referred to as 'secondary findings'. In this report, we analyze the prevalence of blended phenotypes in a cohort of 447 individuals who underwent broad genomic sequencing and also present a case series of eight probands who presented multiple diagnoses, generating a mixed phenotype and creating a peculiar clinical situation. In total, 3.86% (8/207) were found to have blended phenotypes, which would have been missed had those individuals not undergone comprehensive genetic testing. We reflect upon the clinical complexity of such cases and explore the consequences of the use of broad sequencing strategies in clinical practice, particularly focusing on the potential to provide a more complete diagnostic scenario. By acknowledging and understanding the complexities of blended phenotypes, clinicians can adopt a more nuanced and tailored approach to patient care.

American Journal of Medical Genetics Part AVol. 197(12)
Hospital Universitário de Santa Maria (BR), National Center for Global Health and Medicine (JP), Yokohama City University Hospital (JP), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Yokohama City University (JP)
Takeda Science Foundation, Japan Agency for Medical Research and Development, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Japan Society for the Promotion of Science
Openalex Percentile: Top 78%
Genomics and Rare Diseases
DOISourceOpenAlex
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