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Next-generation sequencing in X-linked intellectual disability

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Next-generation sequencing in X-linked intellectual disability. / Tzschach, Andreas; Grasshoff, Ute; Beck-Woedl, Stefanie; Dufke, Claudia; Bauer, Claudia; Kehrer, Martin; Evers, Christina; Moog, Ute; Oehl-Jaschkowitz, Barbara; Di Donato, Nataliya; Maiwald, Robert; Jung, Christine; Kuechler, Alma; Schulz, Solveig; Meinecke, Peter; Spranger, Stephanie; Kohlhase, Jürgen; Seidel, Jörg; Reif, Silke; Rieger, Manuela; Riess, Angelika; Sturm, Marc; Bickmann, Julia; Schroeder, Christopher; Dufke, Andreas; Riess, Olaf; Bauer, Peter.

In: EUR J HUM GENET, Vol. 23, No. 11, 10.2015, p. 1513-8.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Tzschach, A, Grasshoff, U, Beck-Woedl, S, Dufke, C, Bauer, C, Kehrer, M, Evers, C, Moog, U, Oehl-Jaschkowitz, B, Di Donato, N, Maiwald, R, Jung, C, Kuechler, A, Schulz, S, Meinecke, P, Spranger, S, Kohlhase, J, Seidel, J, Reif, S, Rieger, M, Riess, A, Sturm, M, Bickmann, J, Schroeder, C, Dufke, A, Riess, O & Bauer, P 2015, 'Next-generation sequencing in X-linked intellectual disability', EUR J HUM GENET, vol. 23, no. 11, pp. 1513-8. https://doi.org/10.1038/ejhg.2015.5

APA

Tzschach, A., Grasshoff, U., Beck-Woedl, S., Dufke, C., Bauer, C., Kehrer, M., Evers, C., Moog, U., Oehl-Jaschkowitz, B., Di Donato, N., Maiwald, R., Jung, C., Kuechler, A., Schulz, S., Meinecke, P., Spranger, S., Kohlhase, J., Seidel, J., Reif, S., ... Bauer, P. (2015). Next-generation sequencing in X-linked intellectual disability. EUR J HUM GENET, 23(11), 1513-8. https://doi.org/10.1038/ejhg.2015.5

Vancouver

Tzschach A, Grasshoff U, Beck-Woedl S, Dufke C, Bauer C, Kehrer M et al. Next-generation sequencing in X-linked intellectual disability. EUR J HUM GENET. 2015 Oct;23(11):1513-8. https://doi.org/10.1038/ejhg.2015.5

Bibtex

@article{aa9934d1ea4e4c63aad8571a7e49f1ce,
title = "Next-generation sequencing in X-linked intellectual disability",
abstract = "X-linked intellectual disability (XLID) is a genetically heterogeneous disorder with more than 100 genes known to date. Most genes are responsible for a small proportion of patients only, which has hitherto hampered the systematic screening of large patient cohorts. We performed targeted enrichment and next-generation sequencing of 107 XLID genes in a cohort of 150 male patients. Hundred patients had sporadic intellectual disability, and 50 patients had a family history suggestive of XLID. We also analysed a sporadic female patient with severe ID and epilepsy because she had strongly skewed X-inactivation. Target enrichment and high parallel sequencing allowed a diagnostic coverage of >10 reads for ~96% of all coding bases of the XLID genes at a mean coverage of 124 reads. We found 18 pathogenic variants in 13 XLID genes (AP1S2, ATRX, CUL4B, DLG3, IQSEC2, KDM5C, MED12, OPHN1, SLC9A6, SMC1A, UBE2A, UPF3B and ZDHHC9) among the 150 male patients. Thirteen pathogenic variants were present in the group of 50 familial patients (26%), and 5 pathogenic variants among the 100 sporadic patients (5%). Systematic gene dosage analysis for low coverage exons detected one pathogenic hemizygous deletion. An IQSEC2 nonsense variant was detected in the female ID patient, providing further evidence for a role of this gene in encephalopathy in females. Skewed X-inactivation was more frequently observed in mothers with pathogenic variants compared with those without known X-linked defects. The mutation rate in the cohort of sporadic patients corroborates previous estimates of 5-10% for X-chromosomal defects in male ID patients.",
author = "Andreas Tzschach and Ute Grasshoff and Stefanie Beck-Woedl and Claudia Dufke and Claudia Bauer and Martin Kehrer and Christina Evers and Ute Moog and Barbara Oehl-Jaschkowitz and {Di Donato}, Nataliya and Robert Maiwald and Christine Jung and Alma Kuechler and Solveig Schulz and Peter Meinecke and Stephanie Spranger and J{\"u}rgen Kohlhase and J{\"o}rg Seidel and Silke Reif and Manuela Rieger and Angelika Riess and Marc Sturm and Julia Bickmann and Christopher Schroeder and Andreas Dufke and Olaf Riess and Peter Bauer",
year = "2015",
month = oct,
doi = "10.1038/ejhg.2015.5",
language = "English",
volume = "23",
pages = "1513--8",
journal = "EUR J HUM GENET",
issn = "1018-4813",
publisher = "NATURE PUBLISHING GROUP",
number = "11",

}

RIS

TY - JOUR

T1 - Next-generation sequencing in X-linked intellectual disability

AU - Tzschach, Andreas

AU - Grasshoff, Ute

AU - Beck-Woedl, Stefanie

AU - Dufke, Claudia

AU - Bauer, Claudia

AU - Kehrer, Martin

AU - Evers, Christina

AU - Moog, Ute

AU - Oehl-Jaschkowitz, Barbara

AU - Di Donato, Nataliya

AU - Maiwald, Robert

AU - Jung, Christine

AU - Kuechler, Alma

AU - Schulz, Solveig

AU - Meinecke, Peter

AU - Spranger, Stephanie

AU - Kohlhase, Jürgen

AU - Seidel, Jörg

AU - Reif, Silke

AU - Rieger, Manuela

AU - Riess, Angelika

AU - Sturm, Marc

AU - Bickmann, Julia

AU - Schroeder, Christopher

AU - Dufke, Andreas

AU - Riess, Olaf

AU - Bauer, Peter

PY - 2015/10

Y1 - 2015/10

N2 - X-linked intellectual disability (XLID) is a genetically heterogeneous disorder with more than 100 genes known to date. Most genes are responsible for a small proportion of patients only, which has hitherto hampered the systematic screening of large patient cohorts. We performed targeted enrichment and next-generation sequencing of 107 XLID genes in a cohort of 150 male patients. Hundred patients had sporadic intellectual disability, and 50 patients had a family history suggestive of XLID. We also analysed a sporadic female patient with severe ID and epilepsy because she had strongly skewed X-inactivation. Target enrichment and high parallel sequencing allowed a diagnostic coverage of >10 reads for ~96% of all coding bases of the XLID genes at a mean coverage of 124 reads. We found 18 pathogenic variants in 13 XLID genes (AP1S2, ATRX, CUL4B, DLG3, IQSEC2, KDM5C, MED12, OPHN1, SLC9A6, SMC1A, UBE2A, UPF3B and ZDHHC9) among the 150 male patients. Thirteen pathogenic variants were present in the group of 50 familial patients (26%), and 5 pathogenic variants among the 100 sporadic patients (5%). Systematic gene dosage analysis for low coverage exons detected one pathogenic hemizygous deletion. An IQSEC2 nonsense variant was detected in the female ID patient, providing further evidence for a role of this gene in encephalopathy in females. Skewed X-inactivation was more frequently observed in mothers with pathogenic variants compared with those without known X-linked defects. The mutation rate in the cohort of sporadic patients corroborates previous estimates of 5-10% for X-chromosomal defects in male ID patients.

AB - X-linked intellectual disability (XLID) is a genetically heterogeneous disorder with more than 100 genes known to date. Most genes are responsible for a small proportion of patients only, which has hitherto hampered the systematic screening of large patient cohorts. We performed targeted enrichment and next-generation sequencing of 107 XLID genes in a cohort of 150 male patients. Hundred patients had sporadic intellectual disability, and 50 patients had a family history suggestive of XLID. We also analysed a sporadic female patient with severe ID and epilepsy because she had strongly skewed X-inactivation. Target enrichment and high parallel sequencing allowed a diagnostic coverage of >10 reads for ~96% of all coding bases of the XLID genes at a mean coverage of 124 reads. We found 18 pathogenic variants in 13 XLID genes (AP1S2, ATRX, CUL4B, DLG3, IQSEC2, KDM5C, MED12, OPHN1, SLC9A6, SMC1A, UBE2A, UPF3B and ZDHHC9) among the 150 male patients. Thirteen pathogenic variants were present in the group of 50 familial patients (26%), and 5 pathogenic variants among the 100 sporadic patients (5%). Systematic gene dosage analysis for low coverage exons detected one pathogenic hemizygous deletion. An IQSEC2 nonsense variant was detected in the female ID patient, providing further evidence for a role of this gene in encephalopathy in females. Skewed X-inactivation was more frequently observed in mothers with pathogenic variants compared with those without known X-linked defects. The mutation rate in the cohort of sporadic patients corroborates previous estimates of 5-10% for X-chromosomal defects in male ID patients.

U2 - 10.1038/ejhg.2015.5

DO - 10.1038/ejhg.2015.5

M3 - SCORING: Journal article

C2 - 25649377

VL - 23

SP - 1513

EP - 1518

JO - EUR J HUM GENET

JF - EUR J HUM GENET

SN - 1018-4813

IS - 11

ER -