Genotype-phenotype correlation in 22q11.2 deletion syndrome
<p>Abstract</p> <p>Background</p> <p>The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively...
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| Format: | Article |
| Language: | English |
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BMC
2012-12-01
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| Series: | BMC Medical Genetics |
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| Online Access: | http://www.biomedcentral.com/1471-2350/13/122 |
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| author | Michaelovsky Elena Frisch Amos Carmel Miri Patya Miriam Zarchi Omer Green Tamar Basel-Vanagaite Lina Weizman Abraham Gothelf Doron |
| author_facet | Michaelovsky Elena Frisch Amos Carmel Miri Patya Miriam Zarchi Omer Green Tamar Basel-Vanagaite Lina Weizman Abraham Gothelf Doron |
| author_sort | Michaelovsky Elena |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion.</p> <p>Methods</p> <p>Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation.</p> <p>Results</p> <p>Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted.</p> <p>Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes.</p> <p>Conclusions</p> <p>MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms.</p> <p>Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.</p> |
| first_indexed | 2024-12-14T03:59:11Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2350 |
| language | English |
| last_indexed | 2024-12-14T03:59:11Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
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| series | BMC Medical Genetics |
| spelling | doaj.art-6a06f6960e7d4eeca7b130be8f80cbf02022-12-21T23:18:01ZengBMCBMC Medical Genetics1471-23502012-12-0113112210.1186/1471-2350-13-122Genotype-phenotype correlation in 22q11.2 deletion syndromeMichaelovsky ElenaFrisch AmosCarmel MiriPatya MiriamZarchi OmerGreen TamarBasel-Vanagaite LinaWeizman AbrahamGothelf Doron<p>Abstract</p> <p>Background</p> <p>The 22q11.2 deletion syndrome (22q11.2DS) is caused by hemizygous microdeletions on chromosome 22q11.2 with highly variable physical and neuropsychiatric manifestations. We explored the genotype-phenotype relationship in a relatively large 22q11.2DS cohort treated and monitored in our clinic using comprehensive clinical evaluation and detailed molecular characterization of the deletion.</p> <p>Methods</p> <p>Molecular analyses in 142 subjects with 22q11.2DS features were performed by FISH and MLPA methods. Participants underwent clinical assessment of physical symptoms and structured psychiatric and cognitive evaluation.</p> <p>Results</p> <p>Deletions were found in 110 individuals including one with an atypical nested distal deletion which was missed by the FISH test. Most subjects (88.2%) carried the 3Mb typically deleted region and 11.8% carried 4 types of deletions differing in size and location. No statistically significant genotype-phenotype correlations were found between deletion type and clinical data although some differences in hypocalcemia and cardiovascular anomalies were noted.</p> <p>Analysis of the patient with the distal nested deletion suggested a redundancy of genes causing the physical and neuropsychiatric phenotype in 22q11.2DS and indicating that the psychiatric and cognitive trajectories may be governed by different genes.</p> <p>Conclusions</p> <p>MLPA is a useful and affordable molecular method combining accurate diagnosis and detailed deletion characterization. Variations in deletion type and clinical manifestations impede the detection of significant differences in samples of moderate size, but analysis of individuals with unique deletions may provide insight into the underlying biological mechanisms.</p> <p>Future genotype-phenotype studies should involve large multicenter collaborations employing uniform clinical standards and high-resolution molecular methods.</p>http://www.biomedcentral.com/1471-2350/13/122Velocardiofacial syndrome (VCFS)Multiplex ligation probe amplification (MLPA)Copy number variation (CNV)Molecular diagnosisNeuropsychiatric disorders |
| spellingShingle | Michaelovsky Elena Frisch Amos Carmel Miri Patya Miriam Zarchi Omer Green Tamar Basel-Vanagaite Lina Weizman Abraham Gothelf Doron Genotype-phenotype correlation in 22q11.2 deletion syndrome BMC Medical Genetics Velocardiofacial syndrome (VCFS) Multiplex ligation probe amplification (MLPA) Copy number variation (CNV) Molecular diagnosis Neuropsychiatric disorders |
| title | Genotype-phenotype correlation in 22q11.2 deletion syndrome |
| title_full | Genotype-phenotype correlation in 22q11.2 deletion syndrome |
| title_fullStr | Genotype-phenotype correlation in 22q11.2 deletion syndrome |
| title_full_unstemmed | Genotype-phenotype correlation in 22q11.2 deletion syndrome |
| title_short | Genotype-phenotype correlation in 22q11.2 deletion syndrome |
| title_sort | genotype phenotype correlation in 22q11 2 deletion syndrome |
| topic | Velocardiofacial syndrome (VCFS) Multiplex ligation probe amplification (MLPA) Copy number variation (CNV) Molecular diagnosis Neuropsychiatric disorders |
| url | http://www.biomedcentral.com/1471-2350/13/122 |
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