Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10 362 consecutive cases

被引：37

作者：

Pham, Justin ^{[1
]}

Shaw, Chad ^{[1
]}

Pursley, Amber ^{[1
]}

Hixson, Patricia ^{[1
]}

Sampath, Srirangan ^{[1
]}

Roney, Erin ^{[1
]}

Gambin, Tomasz ^{[1
]}

Kang, Sung-Hae L. ^{[2
]}

Bi, Weimin ^{[1
]}

Lalani, Seema ^{[1
,3
]}

Bacino, Carlos ^{[1
,3
]}

Lupski, James R. ^{[1
,3
,4
]}

Stankiewicz, Pawel ^{[1
]}

Patel, Ankita ^{[1
]}

Cheung, Sau-Wai ^{[1
]}

机构：

[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[2] Allina Med Labs, Minneapolis, MN USA

[3] Texas Childrens Hosp, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2014年 / 22卷 / 08期

关键词：

somatic mosaicism; array CGH; CNV; chromosomal structural abnormalities; mosaic exon deletion; PALLISTER-KILLIAN-SYNDROME; DNA-REPLICATION MECHANISM; RING CHROMOSOME FORMATION; ARRAY CGH; ABERRATIONS; DELETION; TRISOMY; BLOOD;

D O I：

10.1038/ejhg.2013.285

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Somatic chromosomal mosaicism arising from post-zygotic errors is known to cause several well-defined genetic syndromes as well as contribute to phenotypic variation in diseases. However, somatic mosaicism is often under-diagnosed due to challenges in detection. We evaluated 10 362 patients with a custom-designed, exon-targeted whole-genome oligonucleotide array and detected somatic mosaicism in a total of 57 cases (0.55%). The mosaicism was characterized and confirmed by fluorescence in situ hybridization (FISH) and/or chromosome analysis. Different categories of abnormal cell lines were detected: (1) aneuploidy, including sex chromosome abnormalities and isochromosomes (22 cases), (2) ring or marker chromosomes (12 cases), (3) single deletion/duplication copy number variations (CNVs) (11 cases), (4) multiple deletion/duplication CNVs (5 cases), (5) exonic CNVs (4 cases), and (6) unbalanced translocations (3 cases). Levels of mosaicism calculated based on the array data were in good concordance with those observed by FISH (10-93%). Of the 14 cases evaluated concurrently by chromosome analysis, mosaicism was detected solely by the array in 4 cases (29%). In summary, our exon-targeted array further expands the diagnostic capability of high-resolution array comparative genomic hybridization in detecting mosaicism for cytogenetic abnormalities as well as small CNVs in disease-causing genes.

引用

页码：969 / 978

页数：10

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