Mosaicism in 22q11.2 Microdeletion Syndrome
Introduction: Microdeletion syndrome is characterized by sub-microscopic chromosomal deletion smaller than 5 Million bp (5Mb) and frequently associated with multiple congenital anomalies. Fluorescent In Situ Hybridization (FISH), Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
JCDR Research and Publications Private Limited
2018-11-01
|
| Series: | Journal of Clinical and Diagnostic Research |
| Subjects: | |
| Online Access: | https://jcdr.net/articles/PDF/12234/37540_CE(RA1)_F(AP)_PF1(AGAK)_PFA(AK)_PBNC(AG)_PN(SHU).pdf |
| _version_ | 1819104357943083008 |
|---|---|
| author | Ashutosh Halder Manish Jain Amanpreet Kaur Kalsi |
| author_facet | Ashutosh Halder Manish Jain Amanpreet Kaur Kalsi |
| author_sort | Ashutosh Halder |
| collection | DOAJ |
| description | Introduction: Microdeletion syndrome is characterized by sub-microscopic chromosomal deletion smaller than 5 Million bp (5Mb) and frequently associated with multiple congenital anomalies. Fluorescent In Situ Hybridization (FISH), Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative Fluorescence Polymerase Chain Reaction (QFPCR), array Comparative Genomic Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) microarray and Next-Generation Sequencing (NGS) techniques are commonly used for precise genetic diagnosis of microdeletion syndrome. Aim: To study the role of mosaicism for the causation of phenotypic heterogeneity in 22q11.2 microdeletion syndrome. Materials and Methods: In this study, for over the period of 10 years, we worked on detection of 22q11.2 microdeletion and observed mosaicism frequently. FISH analysis was used to assess level of mosaicism in metaphase and interphase cells derived from peripheral blood culture (lymphocytes) and interphase cells of various tissues like blood nucleated cells (mesodermal origin), buccal cells (ectodermal origin) and urinary exfoliated cells (endodermal origin). We have also used SNP microarray and QF PCR for further characterization. Results: Among 257 cases of clinically suspected 22q11.2 microdeletion syndrome, presence of 22q11.2 microdeletion was confirmed in 39 cases (15.2%) by FISH. Eleven of 22q11.2 microdeletion cases (28.2%) were found to have mosaicism. We report high (28.2%) prevalence of mosaicism in 22q11.2 microdeletion syndrome and often (about 36% cases) low grade mosaicism (<35% deleted cells). Outsourced SNP microarray failed to detect low grade mosaicism. We also observed wide variations in deleted cell concentration amongst various tissues (blood, buccal and urinary cells). Conclusion: We conclude that mosaicism in 22q11.2 microdeletion is common (28.2%) and interphase FISH should be the choice of test for detecting mosaicism. |
| first_indexed | 2024-12-22T02:05:05Z |
| format | Article |
| id | doaj.art-11c97081242e49139a9fa8915a26ff29 |
| institution | Directory Open Access Journal |
| issn | 2249-782X 0973-709X |
| language | English |
| last_indexed | 2024-12-22T02:05:05Z |
| publishDate | 2018-11-01 |
| publisher | JCDR Research and Publications Private Limited |
| record_format | Article |
| series | Journal of Clinical and Diagnostic Research |
| spelling | doaj.art-11c97081242e49139a9fa8915a26ff292022-12-21T18:42:33ZengJCDR Research and Publications Private LimitedJournal of Clinical and Diagnostic Research2249-782X0973-709X2018-11-011211GC01GC0610.7860/JCDR/2018/37540.12234Mosaicism in 22q11.2 Microdeletion SyndromeAshutosh Halder0Manish Jain1Amanpreet Kaur Kalsi2Professor and Head, Department of Reproductive Biology, AIIMS, New Delhi, India.Scientist, Department of Reproductive Biology, AIIMS, New Delhi, India.PhD Student, Department of Reproductive Biology, AIIMS, New Delhi, India.Introduction: Microdeletion syndrome is characterized by sub-microscopic chromosomal deletion smaller than 5 Million bp (5Mb) and frequently associated with multiple congenital anomalies. Fluorescent In Situ Hybridization (FISH), Multiplex Ligation-Dependent Probe Amplification (MLPA), Quantitative Fluorescence Polymerase Chain Reaction (QFPCR), array Comparative Genomic Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) microarray and Next-Generation Sequencing (NGS) techniques are commonly used for precise genetic diagnosis of microdeletion syndrome. Aim: To study the role of mosaicism for the causation of phenotypic heterogeneity in 22q11.2 microdeletion syndrome. Materials and Methods: In this study, for over the period of 10 years, we worked on detection of 22q11.2 microdeletion and observed mosaicism frequently. FISH analysis was used to assess level of mosaicism in metaphase and interphase cells derived from peripheral blood culture (lymphocytes) and interphase cells of various tissues like blood nucleated cells (mesodermal origin), buccal cells (ectodermal origin) and urinary exfoliated cells (endodermal origin). We have also used SNP microarray and QF PCR for further characterization. Results: Among 257 cases of clinically suspected 22q11.2 microdeletion syndrome, presence of 22q11.2 microdeletion was confirmed in 39 cases (15.2%) by FISH. Eleven of 22q11.2 microdeletion cases (28.2%) were found to have mosaicism. We report high (28.2%) prevalence of mosaicism in 22q11.2 microdeletion syndrome and often (about 36% cases) low grade mosaicism (<35% deleted cells). Outsourced SNP microarray failed to detect low grade mosaicism. We also observed wide variations in deleted cell concentration amongst various tissues (blood, buccal and urinary cells). Conclusion: We conclude that mosaicism in 22q11.2 microdeletion is common (28.2%) and interphase FISH should be the choice of test for detecting mosaicism.https://jcdr.net/articles/PDF/12234/37540_CE(RA1)_F(AP)_PF1(AGAK)_PFA(AK)_PBNC(AG)_PN(SHU).pdffluorescent in situ hybridizationinterphase cellssingle nucleotide polymorphism microarray |
| spellingShingle | Ashutosh Halder Manish Jain Amanpreet Kaur Kalsi Mosaicism in 22q11.2 Microdeletion Syndrome Journal of Clinical and Diagnostic Research fluorescent in situ hybridization interphase cells single nucleotide polymorphism microarray |
| title | Mosaicism in 22q11.2 Microdeletion Syndrome |
| title_full | Mosaicism in 22q11.2 Microdeletion Syndrome |
| title_fullStr | Mosaicism in 22q11.2 Microdeletion Syndrome |
| title_full_unstemmed | Mosaicism in 22q11.2 Microdeletion Syndrome |
| title_short | Mosaicism in 22q11.2 Microdeletion Syndrome |
| title_sort | mosaicism in 22q11 2 microdeletion syndrome |
| topic | fluorescent in situ hybridization interphase cells single nucleotide polymorphism microarray |
| url | https://jcdr.net/articles/PDF/12234/37540_CE(RA1)_F(AP)_PF1(AGAK)_PFA(AK)_PBNC(AG)_PN(SHU).pdf |
| work_keys_str_mv | AT ashutoshhalder mosaicismin22q112microdeletionsyndrome AT manishjain mosaicismin22q112microdeletionsyndrome AT amanpreetkaurkalsi mosaicismin22q112microdeletionsyndrome |