Evaluation of Genetic Testing in a Cohort of Diverse Pediatric Patients in the United States with Congenital Cataracts
Abstract
:1. Introduction
2. Materials and Methods
2.1. Clinical Assessment
2.2. Molecular Investigations
2.3. Analysis
3. Results
3.1. Microarray Results
3.2. Targeted Genetic Testing for Ocular Phenotypes
3.3. Whole Exome Sequencing/Expanded Testing
3.4. Genetic Testing for Other Systemic Phenotypes
3.5. Functional Enrichment Analysis of Variant Genes
3.6. Variant Reclassification
4. Discussion
4.1. Diagnostic Yield
4.2. Inconclusive/Negative Results
4.3. GO Enrichment Analysis
4.4. Variant Reclassification
4.5. Future Research Aims
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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N (%) | |
---|---|
Race/Ethnicity | |
White | 22 (42%) |
Hispanic | 19 (37%) |
Black | 4 (8%) |
Asian | 3 (6%) |
Other | 4 (8%) |
Systemic Illness | |
Yes | 40 (77%) |
No | 12 (23%) |
Family History | |
Yes | 4 (8%) |
No | 48 (92%) |
Lensectomy | |
No | 22 (42%) |
Yes | 30 (58%) |
Unilateral | 5 (17%) |
Bilateral | 25 (83%) |
<1 year-old | 16 (53%) |
1–10 years-old | 8 (27%) |
>10 years-old | 6 (20%) |
Patient # | Date of Test | Microarray Findings | Diagnostic Yield Positive |
---|---|---|---|
1 | 2011 | 11p14.3p11.2(25,958,860–43,778,471)×1 | Yes |
2 | 2013 | 7q31.1(110,950,859–111,234,120)×1 | No |
3 | 2020 | 21q22.12q22.13(35,903,896–39,545,357)×1 | Yes |
4 | 2021 | 2p25.3(1,741,827–1,842,843)×3 | No |
5 | 2016 | 7q35(146,051,998–147,171,974)×3 7q35q36.3(147,171,974–159,138,663)×1 | No |
6 | 2010 | 22q11.22(20,640,000–20,905,000)×1 | No |
7 | 2019 | Normal | No |
8 | 2009 | Normal | No |
9 | 2011 | Normal | No |
10 | 2016 | Normal | No |
11 | 2018 | Normal | No |
12 | 2014 | Normal | No |
13 | 2010 | Normal | No |
14 | 2008 | Normal | No |
15 | 2020 | Normal | No |
16 | 2012 | Normal | No |
17 | 2005 | Normal | No |
18 | 2011 | Normal | No |
Patient # | Test (Laboratory) | Date of Test | Gene (Variant Classification) | Diagnostic Yield Positive |
---|---|---|---|---|
19 | Comprehensive Cataracts Panel (Prevention Genetics) | 2020 | CAPN15 (VUS), CYP27A1 (VUS), FYCO1 (VUS) | No |
20 | Early-Onset Bilateral Cataracts Panel (Prevention Genetics) | 2021 | CRYBB2 (VUS) | No |
21 | Comprehensive Cataracts Panel (Prevention Genetics) | 2021 | INPP5B (VUS), LTBP2 (VUS), POMT2 (VUS) | No |
22 | Microphthalmia, Anophthalmia, and Anterior Segment Dysgenesis Gene Panel (Blueprint Genetics) | 2019 | PAX6 (LP) | Yes |
23 | Comprehensive Cataracts Panel (Prevention Genetics) | 2019 | NHS (P) | Yes |
24 | PAX6 Gene/Aniridia/Developmental Eye Disorders (GeneDx) | 2019 | 11p13 deletion (P) | Yes |
25 | Comprehensive Cataract Panel (Prevention Genetics) | 2021 | RAB3GAP1 (LP), RAB3GAP1 (VUS), BFSP1 (VUS), BFSP1 (VUS), ADAMTS10 (VUS), AGPS (VUS), ERCC1 (VUS) | Yes |
26 | Early-Onset Bilateral Cataracts Panel (Prevention Genetics) | 2021 | COL18A1 (VUS), GALK1 (VUS) | No |
27 | PAX6 Sequencing (Emory Genetics Laboratory) | 2015 | PAX6 (P) | Yes |
28 | Microphthalmia, Anophthalmia, and Anterior Segment Dysgenesis Gene Panel (Blueprint Genetics) | 2020 | No P, LP or VUS | No |
29 | :Custom sequencing panel with CNV detection for Coloboma Genes (Prevention Genetics) | 2018 | No P, LP or VUS | No |
30 | Cataract Panel (Invitae) | 2022 | CRYAA (P), CRYBB1 ((VUS) | Yes |
31 | Early-Onset Bilateral Cataracts Panel (Prevention Genetics) | 2022 | ERCC2 (VUS), ERCC2 (VUS) | No |
Patient # | Test (Laboratory) | Date of Test | Gene (Variant Classification) | Diagnostic Yield Positive |
---|---|---|---|---|
32 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2019 | PHACTR4 (VUS) | No |
33 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2016 | ALDH18A1 (LP) | Yes |
34 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2017 | DYNC1H1 (LP), LRP5 (VUS) | Yes |
35 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2020 | KIF1A (P) | Yes |
36 | XomeDx [WES] (GeneDx) | 2014 | BCOR (LP/P), ATP2A3 (VUS) | Yes |
37 | XomeDx [WES] (GeneDx) | 2014 | BCOR (LP.P) | Yes |
38 | XomeDx Reanalysis (GeneDx) | 2021 | No P, LP or VUS | No |
39 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2019 | No P, LP or VUS | No |
40 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2017 | SYNE1 (P), AAAS (P) | Inconclusive |
41 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2018 | PIK3R1 (VUS) | No |
42 | Cerebral Palsy Spectrum Disorders Panel (Invitae) & XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2021 | RARB (LP) | Yes |
43 | XomeDx Plus [WES + mitochondrial genome analyses] (GeneDx) | 2021 | WDPCP (VUS), WDPCP (VUS) | Inconclusive |
44 | XomeDx [WES] (GeneDx) | 2022 | 13q12.11 duplication which includes GJA3 (VUS) | Inconclusive |
Patient # | Test (Laboratory) | Date of Test | Gene (Variant Classification) | Diagnostic Yield Positive |
---|---|---|---|---|
46 | Dystroglycan-Related Congenital Muscular Dystrophy Panel (Prevention Genetics) | 2019 | POMT1 (P) | Yes |
47 | Cholestasis Panel (EGL Genetics) | 2017 | NOTCH2 (VUS) | Inconclusive |
48 | Autism/ID Xpanded Panel (GeneDx) | 2019 | CSNK2B (LP), KCNB1 (LP) | No |
49 | Comprehensive Epilepsy Panel (Lurie Molecular Diagnostic Laboratory) & ExomeNext [WES] (Ambry Genetics) | 2018 | NR4A2 (P), DYNC1H1 (VUS), PNKP (VUS), SCN2A (VUS) | Inconclusive |
50 | GRB10 gene to confirm variant identified in lab (GeneDx | 2014 | GRB10 (LP/P) | No |
51 | NGLY1 evaluation for research found variant (GeneDx) | 2015 | NGLY1 (LP/P) | No |
52 | PGL/PCC panel, evaluating for familial variant (GeneDx) | 2013 | SDHD (LP/P) | Inconclusive |
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Rossen, J.L.; Bohnsack, B.L.; Zhang, K.X.; Ing, A.; Drackley, A.; Castelluccio, V.; Ralay-Ranaivo, H. Evaluation of Genetic Testing in a Cohort of Diverse Pediatric Patients in the United States with Congenital Cataracts. Genes 2023, 14, 608. https://doi.org/10.3390/genes14030608
Rossen JL, Bohnsack BL, Zhang KX, Ing A, Drackley A, Castelluccio V, Ralay-Ranaivo H. Evaluation of Genetic Testing in a Cohort of Diverse Pediatric Patients in the United States with Congenital Cataracts. Genes. 2023; 14(3):608. https://doi.org/10.3390/genes14030608
Chicago/Turabian StyleRossen, Jennifer L., Brenda L. Bohnsack, Kevin X. Zhang, Alexander Ing, Andy Drackley, Valerie Castelluccio, and Hanta Ralay-Ranaivo. 2023. "Evaluation of Genetic Testing in a Cohort of Diverse Pediatric Patients in the United States with Congenital Cataracts" Genes 14, no. 3: 608. https://doi.org/10.3390/genes14030608