The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2.

Abstract

Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.

• Authors: Lusine Nazaryan, Eunice G Stefanou, Claus Hansen, Nadezda Kosyakova, Mads Bak, Freddie H Sharkey, Theodora Mantziou, Anastasios D Papanastasiou, Voula Velissariou, Thomas Liehr, Maria Syrrou, Niels Tommerup
• Journal: European journal of human genetics : EJHG (Eur J Hum Genet) Vol. 22 Issue 3 Pg. 338-43 (Mar 2014) ISSN: 1476-5438 [Electronic] England
• PMID: 23860044 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• FOXP2 protein, human
• Forkhead Transcription Factors

Topics

• Child
• Chromosomal Instability
• Chromosomes, Human, Pair 2 (genetics)
• Chromosomes, Human, Pair 5 (genetics)
• Chromosomes, Human, Pair 7 (genetics)
• Cytogenetic Analysis
• Developmental Disabilities (diagnosis, genetics)
• Forkhead Transcription Factors (genetics)
• Germ-Line Mutation
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Sequence Analysis, DNA
• Speech Disorders (diagnosis, genetics)