Overview of the number of variants detected at each filter step for each patient. (DOC 128 kb

Anthonie van Essen (3536792)

Behrooz Alizadeh (3503549)

Birgit Sikkema-Raddatz (3536783)

Conny van Ravenswaaij-Arts (3419003)

Egbert Redeker (3536786)

Hermine Veenstra-Knol (3536771)

Johanna Verheij (3536795)

Krista van Dijk-Bos (3536774)

Lennart Johansson (3009453)

Marcel Mannens (3459431)

Morris Swertz (383290)

Omid Jazayeri (3536789)

Patrick Rump (3536780)

Richard Sinke (3536777)

BMC Medical Genomics

PubMed

Genetic tests performed during the diagnostic work-up of the study participants. (DOC 55 kb

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Additional file 1: Table S1. of Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly

Background: Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed. Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly. Methods: Whole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants. Results: In ten out of these 35 families (29 %), we found mutations in genes already known to be related to a disorder in which microcephaly is a main feature. Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1, RNASEH2B, KIF11, ERCC8, CASK, DYRK1A and BRCA2. In one of the sib-pairs, mutations were found in the RTTN gene. Mutations were present in seven out of our ten families with an established etiological diagnosis with recessive inheritance. Conclusions: We demonstrate that whole-exome sequencing is a powerful tool for the diagnostic evaluation of patients with highly heterogeneous neurodevelopmental disorders such as intellectual disability with microcephaly. Our results confirm that autosomal recessive disorders are highly prevalent among patients with microcephaly

Rump, Patrick

Jazayeri, Omid

van Dijk-Bos, Krista

Johansson, Leonnart F.

van Essen, Anthonie J

Verheij, Johanna B G M

Veenstra-Knol, Hermine E

Redeker, Egbert J W

Mannens, Marcel M A M

Swertz, Morris A

Alizadeh, Behrooz Z

van Ravenswaaij-Arts, Conny M A

Sinke, Richard J

Sikkema-Raddatz, Birgit

NARCIS 

Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly

Background: Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed.Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly.Methods: Whole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants.Results: In ten out of these 35 families (29 %), we found mutations in genes already known to be related to a disorder in which microcephaly is a main feature. Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1, RNASEH2B, KIF11, ERCC8, CASK, DYRK1A and BRCA2. In one of the sib-pairs, mutations were found in the RTTN gene. Mutations were present in seven out of our ten families with an established etiological diagnosis with recessive inheritance.Conclusions: We demonstrate that whole-exome sequencing is a powerful tool for the diagnostic evaluation of patients with highly heterogeneous neurodevelopmental disorders such as intellectual disability with microcephaly. Our results confirm that autosomal recessive disorders are highly prevalent among patients with microcephaly.</p

Dissertations of the University of Groningen

English

Patrick Rump

Omid Jazayeri

Krista K. van Dijk-Bos

Lennart F. Johansson

Anthonie J. van Essen

Johanna B. G. M. Verheij

Hermine E. Veenstra-Knol

Egbert J. W. Redeker

Marcel M. A. M. Mannens

Morris A. Swertz

Behrooz Z. Alizadeh

Conny M. A. van Ravenswaaij-Arts

Richard J. Sinke

Birgit Sikkema-Raddatz

Crossref

ARTS repository - University of Groningen

Proceedings - University of Groningen

Springer - Publisher Connector

Unknown

Texas A&amp;M Repository

Final Review

https://pure.rug.nl/ws/files/41442028/Whole_exome_sequencing_is_a_powerful_approach_for_establishing_the_etiological_diagnosis_in_patients_with_intellectual_disability_and_microcephaly.pdf

Final Review

Abstract

Similar works

Full text

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NARCIS

Dissertations of the University of Groningen

Crossref

ARTS repository - University of Groningen

Proceedings - University of Groningen

ARTS repository - University of Groningen

Proceedings - University of Groningen

Springer - Publisher Connector

Texas A&M Repository

Final Review

Abstract

Similar works

Full text

Available Versions

FigShare

NARCIS

Dissertations of the University of Groningen

Crossref

ARTS repository - University of Groningen

Proceedings - University of Groningen

ARTS repository - University of Groningen

Proceedings - University of Groningen

Springer - Publisher Connector

Texas A&amp;M Repository

Texas A&M Repository