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Open Access 01-12-2015 | Research article

A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations

Authors: Thomas Iype, Vafa Alakbarzade, Mary Iype, Royana Singh, Ajith Sreekantan-Nair, Barry A. Chioza, Tribhuvan M. Mohapatra, Emma L. Baple, Michael A. Patton, Thomas T. Warner, Christos Proukakis, Abhi Kulkarni, Andrew H. Crosby

Published in: BMC Medical Genetics | Issue 1/2015

Abstract

Background

The deletion of the chromosome 4p16.3 Wolf-Hirschhorn syndrome critical region (WHSCR-2) typically results in a characteristic facial appearance, varying intellectual disability, stereotypies and prenatal onset of growth retardation, while gains of the same chromosomal region result in a more variable degree of intellectual deficit and dysmorphism. Similarly the phenotype of individuals with terminal deletions of distal chromosome 3p (3p deletion syndrome) varies from mild to severe intellectual deficit, micro- and trigonocephaly, and a distinct facial appearance.

Methods and results

We investigated a large Indian five-generation pedigree with ten affected family members in which chromosomal microarray and fluorescence in situ hybridization analyses disclosed a complex rearrangement involving chromosomal subregions 4p16.1 and 3p26.3 resulting in a 4p16.1 deletion and 3p26.3 microduplication in three individuals, and a 4p16.1 duplication and 3p26.3 microdeletion in seven individuals. A typical clinical presentation of WHS was observed in all three cases with 4p16.1 deletion and 3p26.3 microduplication. Individuals with a 4p16.1 duplication and 3p26.3 microdeletion demonstrated a range of clinical features including typical 3p microdeletion or 4p partial trisomy syndrome to more severe neurodevelopmental delay with distinct dysmorphic features.

Conclusion

We present the largest pedigree with complex t(4p;3p) chromosomal rearrangements and diverse clinical outcomes including Wolf Hirschorn-, 3p deletion-, and 4p duplication syndrome amongst affected individuals.

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Title: A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations
Authors: Thomas Iype
Vafa Alakbarzade
Mary Iype
Royana Singh
Ajith Sreekantan-Nair
Barry A. Chioza
Tribhuvan M. Mohapatra
Emma L. Baple
Michael A. Patton
Thomas T. Warner
Christos Proukakis
Abhi Kulkarni
Andrew H. Crosby
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2015
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/s12881-015-0251-5

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A large Indian family with rearrangement of chromosome 4p16 and 3p26.3 and divergent clinical presentations

Abstract

Background

Methods and results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods and results

Conclusion

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