Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice
Abstract
:1. Introduction
2. Experimental Section
2.1. Patient Samples
Gene(s) of interest | Number of patients | Clinical indication | Mode of inheritance | Sample type |
---|---|---|---|---|
APC | 7 | Familial adenomatous polyposis (FAP) | Autosomal dominant | Peripheral blood |
Dystrophin ( DMD) | 7 | Becker muscular dystrophy (BMD) | X-linked | Peripheral blood |
17 | Duchenne muscular dystrophy (DMD) | Peripheral blood; Guthrie spot (1) | ||
17 | Carrier testing for BMD/DMD | Peripheral blood | ||
Calcium-sensing receptor (CaSR) | 1 | Familial hypocalciuric hypercalcemia | Autosomal dominant | Peripheral blood |
E-cadherin (CDH1) | 5 | Familial gastric cancer | Autosomal dominant | Peripheral blood |
EPCAM | 3 | Familial colon cancer | Autosomal dominant | Peripheral blood |
HNF4α (MODY1), GCK (MODY2), HNF1α (MODY3), HNF1β (MODY5) | 3 | Maturity-onset diabetes of the young (MODY); 1 individual also with hepatic multiple adenomatosis | Autosomal dominant | Peripheral blood |
PMP22 | 19 | Possible diagnosis of Charcot Marie Tooth Type 1A (CMT1A) | Autosomal dominant | Peripheral blood |
7 | Possible diagnosis of Hereditary Neuropathy with liability to Pressure Palsies (HNPP) | Autosomal dominant | Peripheral blood | |
MSH2 | 2 | Hereditary Non-Polyposis Colorectal Cancer (HNPCC) | Autosomal dominant | Peripheral blood |
PTEN | 3 | Cowden syndrome | Autosomal dominant | Peripheral blood |
RET proto-oncogene, SDHAF2, SDHB, SDHC, SDHD, TMEM127, VHL | 6 | Familial phaeochromocytoma/paraganglioma | Autosomal dominant | Peripheral blood |
1 | Predictive testing for familial paraganglioma | |||
VHL | 1 | Possible diagnosis of Von-Hippel-Lindau syndrome | Autosomal dominant | Peripheral blood |
2.2. DNA Extraction
2.3. Dosage Analysis
3. Results and Discussion
Patient | Gene(s) analysed | Genotype | Significance of result |
---|---|---|---|
1,2 | DMD | Hemizygous deletion of exons 45–47 (inclusive) | In-frame deletion; consistent with BMD phenotype |
3 | Hemizygous deletion of exons 45–48 (inclusive) | In-frame deletion; consistent with BMD phenotype | |
4 | c.5199_5209del (p.Thr1734SerfsX10) | Premature truncation of protein; consistent with DMD phenotype | |
5 | Hemizygous deletion of exons 46–50 (inclusive) | Out-of-frame deletion; consistent with DMD phenotype | |
6 | Hemizygous duplication of exon 12 | Out-of-frame duplication; consistent with DMD phenotype | |
7 | Hemizygous duplication of exons 10–11 (inclusive) | Out-of-frame duplication; consistent with DMD phenotype | |
8 | Hemizygous deletion of exons 53–59 (inclusive) | Out-of-frame deletion; consistent with DMD phenotype | |
9,10 | Hemizygous duplication of exons 8–9 (inclusive) | Out-of-frame duplication; consistent with DMD phenotype | |
11–19 | Various (heterozygous deletion/duplication) | Carrier of familial deletion/duplication | |
20 | HNF1α | Heterozygous deletion of exons 2–3 (inclusive) | Consistent with clinical phenotype—adenomatosis and MODY3 |
21–29 | PMP22 | ~1.5 Mb heterozygous duplication encompassing PMP22 gene | Consistent with CMT1A phenotype |
30,31 | Reciprocal deletion | Consistent with HNPP phenotype | |
32,33 | PTEN | Heterozygous deletion of exon 2 | Consistent with Cowden syndrome phenotype |
34,35 | SDHB | Heterozygous deletion of exon 1 | Consistent with clinical diagnosis of familial phaeo syndrome |
36 | Presence of familial deletion— appropriate surveillance/operative management required |
3.1. PMP22 Gene Analysis—Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP)
3.2. DMD Gene Analysis—Duchenne and Becker Muscular Dystrophy (DMD/BMD)
3.3. PTEN Gene Analysis
3.4. Familial Paraganglioma/Phaeochromocytoma Syndrome Mutation Screening—SDHAF2, SHDB, SDHC, SDHD, VHL, RET Proto-Oncogene, and TMEM127 Gene Analysis
3.5. Maturity-Onset Diabetes of the Young (MODY) Mutation Screening—HNF4α, GCK, HNF1α, HNF1β
4. Conclusions
Acknowledgments
References
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Marquis-Nicholson, R.; Prosser, D.; Love, J.M.; Love, D.R. Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice. Microarrays 2013, 2, 51-62. https://doi.org/10.3390/microarrays2020051
Marquis-Nicholson R, Prosser D, Love JM, Love DR. Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice. Microarrays. 2013; 2(2):51-62. https://doi.org/10.3390/microarrays2020051
Chicago/Turabian StyleMarquis-Nicholson, Renate, Debra Prosser, Jennifer M. Love, and Donald R. Love. 2013. "Gene Dosage Analysis in a Clinical Environment: Gene-Targeted Microarrays as the Platform-of-Choice" Microarrays 2, no. 2: 51-62. https://doi.org/10.3390/microarrays2020051