Hoell, J. I., Gombert, M., Ginzel, S., Loth, S., Landgraf, P., Kaefer, V., Streiter, M., Prokop, A., Weiss, M., Thiele, R. and Borkhardt, A. (2014). Constitutional Mismatch Repair-deficiency and Whole-exome Sequencing as the Means of the Rapid Detection of the Causative MSH6 Defect. Klinische Padiatr., 226 (6-7). S. 357 - 362. STUTTGART: GEORG THIEME VERLAG KG. ISSN 1439-3824

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Abstract

Background: Cases of children with more than one type of cancer either diagnosed simultaneously or successively, rarely occur in pediatric oncology. A second malignant neoplasm may be caused by mutagenic effects of the treatment of the primary malignancy and/or may point towards an underlying genetic cancer susceptibility syndrome. One example of such a syndrome is constitutional mismatch repair-deficiency, (CMMR-D) which carries an increased risk of various tumors including childhood hematologic malignancies and Lynch syndrome associated tumors. Timely diagnosis of CMMR-D is crucial, since this diagnosis has implications for the entire family. Patient: We report the case of a 15-year-old girl who was born to consanguineous parents. At the age of 20 months she was diagnosed with a T-cell non-Hodgkin lymphoma. Treatment was given according to NHL-BFM 95. 12 years later, an invasive adenocarcinoma of the colon was surgically removed which relapsed shortly afterwards. Methods: Whole-exome sequencing of germline DNA was employed to rapidly detect the underlying mutation in this suspected CMMR-D patient. Results: After a short turnaround time of less than 3 weeks, the diagnosis of CMMR-D could be confirmed by the identification of a homozygous 29-bp deletion in MSH6 (exon 6), which was confirmed by independent methods. Conclusions: We demonstrate that bed-side whole-exome sequencing is both feasible and cost-effective and may be the method of choice to rapidly uncover the genetical basis of (inherited) diseases.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hoell, J. I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gombert, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ginzel, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loth, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landgraf, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaefer, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Streiter, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prokop, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiss, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borkhardt, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-423915
DOI: 10.1055/s-0034-1389905
Journal or Publication Title: Klinische Padiatr.
Volume: 226
Number: 6-7
Page Range: S. 357 - 362
Date: 2014
Publisher: GEORG THIEME VERLAG KG
Place of Publication: STUTTGART
ISSN: 1439-3824
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
EUROPEAN CONSORTIUM CARE; NEXT-GENERATION; MUTATIONS; VARIANTS; CANCER; IDENTIFICATION; DISORDERS; CHILDHOODMultiple languages
PediatricsMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42391

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