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The tale of two genes: from next-generation sequencing to phenotype.

ABSTRACT: An 18-yr-old man with a history of intellectual disability, craniofacial dysmorphism, seizure disorder, and obesity was identified to carry a de novo, pathogenic variant in ASXL1 (c.4198G>T; p.E1400X) associated with the diagnosis of Bohring-Opitz syndrome based on exome sequencing. In addition, he was identified to carry a maternally inherited and likely pathogenic variant in MC4R (c.817C>T; p.Q273X) associated with monogenic obesity. Dual genetic diagnosis occurs in 4%-6% of patients and results in unique clinical phenotypes that are a function of tissue-specific gene expression, involved pathways, clinical expressivity, and penetrance. This case highlights the utility of next-generation sequencing in patients with an unusual combination of clinical presentations for several pillars of precision medicine including (1) diagnosis, (2) prognosis and outcome, (3) management and therapy, and (4) utilization of resources.

SUBMITTER: Rohanizadegan M

PROVIDER: S-EPMC7133747 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The tale of two genes: from next-generation sequencing to phenotype.

Rohanizadegan Mersedeh M Siddharath Aishwarya A Retterer Kyle K Hung Christina C Bodamer Olaf O

Cold Spring Harbor molecular case studies 20200401 2

An 18-yr-old man with a history of intellectual disability, craniofacial dysmorphism, seizure disorder, and obesity was identified to carry a de novo, pathogenic variant in <i>ASXL1</i> (c.4198G>T; p.E1400X) associated with the diagnosis of Bohring-Opitz syndrome based on exome sequencing. In addition, he was identified to carry a maternally inherited and likely pathogenic variant in <i>MC4R</i> (c.817C>T; p.Q273X) associated with monogenic obesity. Dual genetic diagnosis occurs in 4%-6% of pati ...[more]

PMID: 31969346

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The tale of two genes: from next-generation sequencing to phenotype.

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The tale of two genes: from next-generation sequencing to phenotype.

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