Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome

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• 作者：Magdalena Koczkowska ; Jolanta Wierzba ; Robert Śmigiel…
• 关键词：22q11.2 deletion syndrome ; Array comparative genomic hybridization ; 17q21.31 microdeletion syndrome ; NF1 microduplication syndrome ; chromosome 6p25.3p25.2 deletion ; NAALADL2
• 刊名：Journal of Applied Genetics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：58
• 期：1
• 页码：93-98
• 全文大小：354KB
• 刊物主题：Plant Genetics & Genomics; Human Genetics; Animal Genetics and Genomics; Microbial Genetics and Genomics;
• 出版者：Springer Berlin Heidelberg
• ISSN：2190-3883
• 卷排序：58

文摘

Chromosome 22q11.2 deletion syndrome, one of the most common human genomic syndromes, has highly heterogeneous clinical presentation. Patients usually harbor a 1.5 to 3 Mb hemizygous deletion at chromosome 22q11.2, resulting in pathognomic TBX1, CRKL and/or MAPK1 haploinsufficiency. However, there are some individuals with clinical features resembling the syndrome who are eventually diagnosed with genomic disorders affecting other chromosomal regions. The objective of this study was to evaluate the additive value of high-resolution array-CGH testing in the cohort of 41 patients with clinical features of 22q11.2 deletion syndrome and negative results of standard cytogenetic diagnostic testing (karyotype and FISH for 22q11.2 locus). Array-CGH analysis revealed no aberrations at chromosomes 22 or 10 allegedly related to the syndrome. Five (12.2 %) patients were found to have other genomic imbalances, namely 17q21.31 microdeletion syndrome (MIM#610443), 1p36 deletion syndrome (MIM#607872), NF1 microduplication syndrome (MIM#613675), chromosome 6pter-p24 deletion syndrome (MIM#612582) and a novel interstitial deletion at 3q26.31 of 0.65 Mb encompassing a dosage-dependent gene NAALADL2. Our study demonstrates that the implementation of array-CGH into the panel of classic diagnostic procedures adds significantly to their efficacy. It allows for detection of constitutional genomic imbalances in 12 % of subjects with negative result of karyotype and FISH targeted for 22q11.2 region. Moreover, if used as first-tier genetic test, the method would provide immediate diagnosis in ∼40 % phenotypic 22q11.2 deletion subjects.