Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect
Microtia is a congenital malformation characterized by a small, abnormally shaped auricle (pinna) ranging in severity. Congenital heart defect (CHD) is one of the comorbid anomalies with microtia. However, the genetic basis of the co-existence of microtia and CHD remains unclear. Copy number variati...
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MDPI AG
2023-04-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/4/879 |
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| author | Caiyun Zhu Yang Yang Bo Pan Hui Wei Jiahang Ju Nuo Si Qi Xu |
| author_facet | Caiyun Zhu Yang Yang Bo Pan Hui Wei Jiahang Ju Nuo Si Qi Xu |
| author_sort | Caiyun Zhu |
| collection | DOAJ |
| description | Microtia is a congenital malformation characterized by a small, abnormally shaped auricle (pinna) ranging in severity. Congenital heart defect (CHD) is one of the comorbid anomalies with microtia. However, the genetic basis of the co-existence of microtia and CHD remains unclear. Copy number variations (CNVs) of 22q11.2 contribute significantly to microtia and CHD, respectively, thus suggesting a possible shared genetic cause embedded in this genomic region. In this study, 19 sporadic patients with microtia and CHD, as well as a nuclear family, were enrolled for genetic screening of single nucleotide variations (SNVs) and CNVs in 22q11.2 by target capture sequencing. We detected a total of 105 potential deleterious variations, which were enriched in ear- or heart-development-related genes, including <i>TBX1</i> and <i>DGCR8</i>. The gene burden analysis also suggested that these genes carry more deleterious mutations in the patients, as well as several other genes associated with cardiac development, such as <i>CLTCL1</i>. Additionally, a microduplication harboring <i>SUSD2</i> was validated in an independent cohort. This study provides new insights into the underlying mechanisms for the comorbidity of microtia and CHD focusing on chromosome 22q11.2, and suggests that a combination of genetic variations, including SNVs and CNVs, may play a crucial role instead of single gene mutation. |
| first_indexed | 2024-03-11T04:58:58Z |
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| id | doaj.art-5b9a6fd1c7704b758023ee163f0d3324 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T04:58:58Z |
| publishDate | 2023-04-01 |
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| series | Genes |
| spelling | doaj.art-5b9a6fd1c7704b758023ee163f0d33242023-11-17T19:23:50ZengMDPI AGGenes2073-44252023-04-0114487910.3390/genes14040879Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart DefectCaiyun Zhu0Yang Yang1Bo Pan2Hui Wei3Jiahang Ju4Nuo Si5Qi Xu6State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, ChinaDepartment of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100144, ChinaDepartment of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100144, ChinaState Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, ChinaState Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, ChinaResearch Center, Plastic Surgery Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100144, ChinaState Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, ChinaMicrotia is a congenital malformation characterized by a small, abnormally shaped auricle (pinna) ranging in severity. Congenital heart defect (CHD) is one of the comorbid anomalies with microtia. However, the genetic basis of the co-existence of microtia and CHD remains unclear. Copy number variations (CNVs) of 22q11.2 contribute significantly to microtia and CHD, respectively, thus suggesting a possible shared genetic cause embedded in this genomic region. In this study, 19 sporadic patients with microtia and CHD, as well as a nuclear family, were enrolled for genetic screening of single nucleotide variations (SNVs) and CNVs in 22q11.2 by target capture sequencing. We detected a total of 105 potential deleterious variations, which were enriched in ear- or heart-development-related genes, including <i>TBX1</i> and <i>DGCR8</i>. The gene burden analysis also suggested that these genes carry more deleterious mutations in the patients, as well as several other genes associated with cardiac development, such as <i>CLTCL1</i>. Additionally, a microduplication harboring <i>SUSD2</i> was validated in an independent cohort. This study provides new insights into the underlying mechanisms for the comorbidity of microtia and CHD focusing on chromosome 22q11.2, and suggests that a combination of genetic variations, including SNVs and CNVs, may play a crucial role instead of single gene mutation.https://www.mdpi.com/2073-4425/14/4/879microtiacongenital heart defecttarget capture sequencing<i>TBX1</i><i>CLTCL1</i> |
| spellingShingle | Caiyun Zhu Yang Yang Bo Pan Hui Wei Jiahang Ju Nuo Si Qi Xu Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect Genes microtia congenital heart defect target capture sequencing <i>TBX1</i> <i>CLTCL1</i> |
| title | Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect |
| title_full | Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect |
| title_fullStr | Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect |
| title_full_unstemmed | Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect |
| title_short | Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect |
| title_sort | genetic screening of targeted region on the chromosome 22q11 2 in patients with microtia and congenital heart defect |
| topic | microtia congenital heart defect target capture sequencing <i>TBX1</i> <i>CLTCL1</i> |
| url | https://www.mdpi.com/2073-4425/14/4/879 |
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