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Exome sequencing in unspecific intellectual disability and rare disorders


Rauch, Anita (2014). Exome sequencing in unspecific intellectual disability and rare disorders. Molecular Cytogenetics, 7(Suppl 1 Pr):I26.

Abstract

Identification of disease causing mutations in genetically heterogeneous conditions such as intellectual disability by Sanger sequencing is time-consuming, costly and often unsuccessful. The advent of NGS techniques is paving the way for novel large scale approaches with an unforeseen diagnostic power. However, the plethora of variants of unknown significance detected by genome-wide approaches requires distinctive strategies to identify actually disease-related mutations. We recently showed that exome sequencing of patient-parent trios in sporadic cases of unspecific severe intellectual disability may unravel disease causing mutation in more than 50% of previously unsolved cases. Thereby it became also evident, that the current descriptions of phenotypes associated with mutations in a certain gene, are heavily biased towards certain recognizable patterns. However, while whole exome sequencing may currently provide theoretically the highest cost-efficient diagnostic power, it may miss mutations due to incomplete coverage of certain genes. Therefore in some phenotypes a “clinical exome” limited to a set of genes with currently known monogenic mutations may also be useful.

Abstract

Identification of disease causing mutations in genetically heterogeneous conditions such as intellectual disability by Sanger sequencing is time-consuming, costly and often unsuccessful. The advent of NGS techniques is paving the way for novel large scale approaches with an unforeseen diagnostic power. However, the plethora of variants of unknown significance detected by genome-wide approaches requires distinctive strategies to identify actually disease-related mutations. We recently showed that exome sequencing of patient-parent trios in sporadic cases of unspecific severe intellectual disability may unravel disease causing mutation in more than 50% of previously unsolved cases. Thereby it became also evident, that the current descriptions of phenotypes associated with mutations in a certain gene, are heavily biased towards certain recognizable patterns. However, while whole exome sequencing may currently provide theoretically the highest cost-efficient diagnostic power, it may miss mutations due to incomplete coverage of certain genes. Therefore in some phenotypes a “clinical exome” limited to a set of genes with currently known monogenic mutations may also be useful.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:21 January 2014
Deposited On:04 Jan 2022 07:01
Last Modified:01 Feb 2022 22:47
Publisher:BioMed Central
ISSN:1755-8166
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1186/1755-8166-7-S1-I26
PubMed ID:24940363
  • Content: Published Version
  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)