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Co‐existence of 9p deletion and Silver‐Russell syndromes in a patient with maternally inherited cryptic complex chromosome rearrangement involving chromosomes 4, 9, and 11
Author(s) -
Hu Jie,
Sathanoori Malini,
Kochmar Sally,
MadanKhetarpal Suneeta,
McGuire Marianne,
Surti Urvashi
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.35658
Subject(s) - gene duplication , chromosomal translocation , comparative genomic hybridization , biology , genetics , breakpoint , derivative chromosome , fluorescence in situ hybridization , chromosome , chromosomal rearrangement , copy number variation , chromosome 17 (human) , chromosome 9 , gene , chromosome 4 , chromosome 22 , karyotype , genome
We report a patient with a maternally inherited unbalanced complex chromosomal rearrangement (CCR) involving chromosomes 4, 9, and 11 detected by microarray comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). This patient presents with clinical features of 9p deletion syndrome and Silver‐Russell syndrome (SRS). Chromosome analysis performed in 2000 showed what appeared to be a simple terminal deletion of chromosome 9p22.1. aCGH performed in 2010 revealed a 1.63 Mb duplication at 4q28.3, a 15.48 Mb deletion at 9p24.3p22.3, and a 1.95 Mb duplication at 11p15.5. FISH analysis revealed a derivative chromosome 9 resulting from an unbalanced translocation between chromosomes 9 and 11, a chromosome 4 fragment inserted near the breakpoint of the translocation. The 4q28.3 duplication does not contain any currently known genes. The 9p24.3p22.3 deletion region contains 36 OMIM genes including a 3.5 Mb critical region for the 9p‐phenotype. The 11p15.5 duplication contains 49 OMIM genes including H19 and IGF2 . Maternal aCGH was normal. However, maternal chromosomal and FISH analyses revealed an apparently balanced CCR involving chromosomes 4, 9, and 11. To the best of our knowledge, this is the first report of a patient with maternally inherited trans ‐duplication of the entire imprinting control region 1 (ICR1) among the 11p15.5 duplications reported in SRS patients. This report supports the hypothesis that the trans ‐duplication of the maternal copy of ICR1 alone is sufficient for the clinical manifestation of SRS and demonstrates the usefulness of combining aCGH with karyotyping and FISH for detecting cryptic genomic imbalances. © 2012 Wiley Periodicals, Inc.