Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program

被引：1

作者：

Bonini, Katherine E. ^{[1
]}

Thomas-Wilson, Amanda ^{[2
]}

Marathe, Priya N. ^{[1
]}

Sebastin, Monisha ^{[3
]}

Odgis, Jacqueline A. ^{[1
]}

Di Biase, Miranda ^{[3
]}

Kelly, Nicole R. ^{[3
]}

Ramos, Michelle A. ^{[4
,5
]}

Insel, Beverly J. ^{[1
]}

Scarimbolo, Laura ^{[1
]}

Rehman, Atteeq U. ^{[2
]}

Guha, Saurav ^{[2
]}

Okur, Volkan ^{[2
]}

Abhyankar, Avinash ^{[2
]}

Phadke, Shruti ^{[2
]}

Nava, Caroline ^{[2
]}

Gallagher, Katie M. ^{[3
,14
]}

Elkhoury, Lama ^{[6
]}

Edelmann, Lisa ^{[6
]}

Zinberg, Randi E. ^{[7
,8
]}

Abul-Husn, Noura S. ^{[1
,7
,9
,15
]}

Diaz, George A. ^{[7
,10
,16
]}

Greally, John M. ^{[3
]}

Suckiel, Sabrina A. ^{[1
,9
]}

Horowitz, Carol R. ^{[4
,5
,9
]}

Kenny, Eimear E. ^{[1
,7
,9
]}

Wasserstein, Melissa ^{[3
]}

Gelb, Bruce D. ^{[7
,10
,11
]}

Jobanputra, Vaidehi ^{[2
,12
,13
]}

机构：

[1] Icahn Sch Med Mt Sinai, Inst Genom Hlth, New York, NY USA

[2] New York Genome Ctr, Mol Diagnost, New York, NY USA

[3] Childrens Hosp Montefiore, Div Pediat Genet Med, Dept Pediat, Montefiore Med Ctr,Albert Einstein Coll Med, Bronx, NY USA

[4] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY USA

[5] Icahn Sch Med Mt Sinai, Inst Hlth Equ Res, New York, NY USA

[6] Sema4, Stamford, CT USA

[7] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA

[8] Icahn Sch Med Mt Sinai, Dept Obstet Gynecol & Reprod Sci, New York, NY USA

[9] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA

[10] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY USA

[11] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA

[12] Columbia Univ Med Ctr, Dept Pathol & Cell Biol, New York, NY USA

[13] New York Genome Ctr, Mol Diagnost, 101 Ave Amer, New York, NY 10013 USA

[14] Sarah Lawrence Coll, Grad Program Human Genet, Bronxville, NY USA

[15] 23andMe Inc, Sunnyvale, CA USA

[16] IECURE Inc, Philadelphia, PA USA

来源：

CLINICAL GENETICS | 2023年 / 104卷 / 02期

关键词：

clinical genomics; CNV; copy number variation; diagnostic testing; diverse populations; genome sequencing; pediatric genomics; JOINT CONSENSUS RECOMMENDATION; CHROMOSOMAL MICROARRAY; MEDICAL GENETICS; AMERICAN-COLLEGE; HAPLOINSUFFICIENCY; MUTATIONS; STANDARDS; DISORDER; CHILDREN; DIVERSE;

D O I：

10.1111/cge.14365

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.

引用

页码：210 / 225

页数：16

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