MLPA for Confirmation of Array CGH Results and Determination of Inheritance

Overview

Journal Mol Cytogenet

Publisher Biomed Central

Specialty Biochemistry

Date 2010 Oct 15

PMID 20942916

Citations 15

Authors

Alison Hills

Joo Wook Ahn

Celia Donaghue

Helen Thomas

Kathy Mann

Caroline Mackie Ogilvie

Affiliations

Soon will be listed here.

Abstract

Background: Array CGH has recently been introduced into our laboratory in place of karyotype analysis for patients with suspected genomic imbalance. Results require confirmation to check sample identity, and analysis of parental samples to determine inheritance and thus assess the clinical significance of the abnormality. Here we describe an MLPA-based strategy for the follow-up of abnormal aCGH results.

Results: In the first 17 months of our MLPA-based aCGH follow-up service, 317 different custom MLPA probes for novel aCGH-detected abnormalities were developed for inheritance studies in 164 families. In addition, 110 samples were tested for confirmation of aCGH-detected abnormalities in common syndromic or subtelomeric regions using commercial MLPA kits. Overall, a total of 1215 samples have been tested by MLPA. A total of 72 de novo abnormalities were confirmed.

Conclusions: Confirmation of aCGH-detected abnormalities and inheritance of these abnormalities are essential for accurate diagnosis and interpretation of aCGH results. The development of a new service utilising custom made MLPA probes and commercial MLPA kits for follow-up studies of array CGH results has been found to be efficient and flexible in our laboratory.

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References

Reddy S, Dolzhanskaya N, Krogh J, Velinov M . A novel 1.4 Mb de novo microdeletion of chromosome 1q21.3 in a child with microcephaly, dysmorphic features and mental retardation. Eur J Med Genet. 2009; 52(6):443-5. DOI: 10.1016/j.ejmg.2009.09.003. View

Pickering D, Eudy J, Olney A, Dave B, Golden D, Stevens J . Array-based comparative genomic hybridization analysis of 1176 consecutive clinical genetics investigations. Genet Med. 2008; 10(4):262-6. DOI: 10.1097/GIM.0b013e31816b64ad. View

Ahn J, Mann K, Docherty Z, Ogilvie C . Submicroscopic chromosome imbalance in patients with developmental delay and/or dysmorphism referred specifically for Fragile X testing and karyotype analysis. Mol Cytogenet. 2008; 1:2. PMC: 2375878. DOI: 10.1186/1755-8166-1-2. View

Miller D, Adam M, Aradhya S, Biesecker L, Brothman A, Carter N . Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet. 2010; 86(5):749-64. PMC: 2869000. DOI: 10.1016/j.ajhg.2010.04.006. View

Li F, Shen Y, Kohler U, Sharkey F, Menon D, Coulleaux L . Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?. Eur J Med Genet. 2010; 53(2):93-9. DOI: 10.1016/j.ejmg.2010.01.004. View

Donaghue C, Roberts A, Mann K, Ogilvie C . Development and targeted application of a rapid QF-PCR test for sex chromosome imbalance. Prenat Diagn. 2003; 23(3):201-10. DOI: 10.1002/pd.569. View

Shinawi M, Liu P, Kang S, Shen J, Belmont J, Scott D . Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2009; 47(5):332-41. PMC: 3158566. DOI: 10.1136/jmg.2009.073015. View

McCarthy S, Makarov V, Kirov G, Addington A, McClellan J, Yoon S . Microduplications of 16p11.2 are associated with schizophrenia. Nat Genet. 2009; 41(11):1223-7. PMC: 2951180. DOI: 10.1038/ng.474. View

Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T . Strong association of de novo copy number mutations with autism. Science. 2007; 316(5823):445-9. PMC: 2993504. DOI: 10.1126/science.1138659. View

10.

Mann K, Fox S, Abbs S, Yau S, Scriven P, Docherty Z . Development and implementation of a new rapid aneuploidy diagnostic service within the UK National Health Service and implications for the future of prenatal diagnosis. Lancet. 2001; 358(9287):1057-61. DOI: 10.1016/S0140-6736(01)06183-9. View

11.

Zhi J, Hatchwell E . Human MLPA Probe Design (H-MAPD): a probe design tool for both electrophoresis-based and bead-coupled human multiplex ligation-dependent probe amplification assays. BMC Genomics. 2008; 9:407. PMC: 2547856. DOI: 10.1186/1471-2164-9-407. View

12.

Miyake N, Shimokawa O, Harada N, Sosonkina N, Okubo A, Kawara H . BAC array CGH reveals genomic aberrations in idiopathic mental retardation. Am J Med Genet A. 2006; 140(3):205-11. DOI: 10.1002/ajmg.a.31098. View

13.

Yu S, Kielt M, Stegner A, Kibiryeva N, Bittel D, Cooley L . Quantitative real-time polymerase chain reaction for the verification of genomic imbalances detected by microarray-based comparative genomic hybridization. Genet Test Mol Biomarkers. 2009; 13(6):751-60. DOI: 10.1089/gtmb.2009.0056. View

14.

Ahn J, Ogilvie C, Welch A, Thomas H, Madula R, Hills A . Detection of subtelomere imbalance using MLPA: validation, development of an analysis protocol, and application in a diagnostic centre. BMC Med Genet. 2007; 8:9. PMC: 1831468. DOI: 10.1186/1471-2350-8-9. View

15.

Schluth C, Gesny R, Borck G, Redon R, Abadie V, Kleinfinger P . New case of interstitial deletion 12(q15-q21.2) in a girl with facial dysmorphism and mental retardation. Am J Med Genet A. 2007; 146A(1):93-6. DOI: 10.1002/ajmg.a.31869. View

16.

Shen Y, Miller D, Cheung S, Lip V, Sheng X, Tomaszewicz K . Development of a focused oligonucleotide-array comparative genomic hybridization chip for clinical diagnosis of genomic imbalance. Clin Chem. 2007; 53(12):2051-9. DOI: 10.1373/clinchem.2007.090290. View

17.

Schouten J, McElgunn C, Waaijer R, Zwijnenburg D, Diepvens F, Pals G . Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002; 30(12):e57. PMC: 117299. DOI: 10.1093/nar/gnf056. View

18.

Jaillard S, Drunat S, Bendavid C, Aboura A, Etcheverry A, Journel H . Identification of gene copy number variations in patients with mental retardation using array-CGH: Novel syndromes in a large French series. Eur J Med Genet. 2009; 53(2):66-75. DOI: 10.1016/j.ejmg.2009.10.002. View

19.

Donaghue C, Mann K, Docherty Z, Mazzaschi R, Fear C, Ogilvie C . Combined QF-PCR and MLPA molecular analysis of miscarriage products: an efficient and robust alternative to karyotype analysis. Prenat Diagn. 2009; 30(2):133-7. DOI: 10.1002/pd.2424. View

20.

Baris H, Tan W, Kimonis V, Irons M . Diagnostic utility of array-based comparative genomic hybridization in a clinical setting. Am J Med Genet A. 2007; 143A(21):2523-33. DOI: 10.1002/ajmg.a.31988. View