A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report
Abstract Background Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infectio...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-023-01765-8 |
| _version_ | 1827581311723765760 |
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| author | Lulu Yan Yan He Yuxin Zhang Yingwen Liu Limin Xu Chunxiao Han Yudan Zhao Haibo Li |
| author_facet | Lulu Yan Yan He Yuxin Zhang Yingwen Liu Limin Xu Chunxiao Han Yudan Zhao Haibo Li |
| author_sort | Lulu Yan |
| collection | DOAJ |
| description | Abstract Background Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population. Case presentation Here, we retrospectively analyzed a case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient’s genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother. Conclusions To our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients. |
| first_indexed | 2024-03-08T22:34:35Z |
| format | Article |
| id | doaj.art-bb4f403d247144d59c120dd8fdfbe667 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-08T22:34:35Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-bb4f403d247144d59c120dd8fdfbe6672023-12-17T12:32:52ZengBMCBMC Medical Genomics1755-87942023-12-011611710.1186/s12920-023-01765-8A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case reportLulu Yan0Yan He1Yuxin Zhang2Yingwen Liu3Limin Xu4Chunxiao Han5Yudan Zhao6Haibo Li7The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children’s HospitalDepartment of Pediatrics, Ningbo Women and Children’s HospitalThe Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children’s HospitalThe Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children’s HospitalDepartment of Pediatrics, Ningbo Women and Children’s HospitalThe Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children’s HospitalDepartment of Pediatrics, Ningbo Women and Children’s HospitalThe Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children’s HospitalAbstract Background Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population. Case presentation Here, we retrospectively analyzed a case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient’s genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother. Conclusions To our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients.https://doi.org/10.1186/s12920-023-01765-8IL7RSevere combined immunodeficiencyWhole exome sequencingChromosome microarray analysisSplicing variant |
| spellingShingle | Lulu Yan Yan He Yuxin Zhang Yingwen Liu Limin Xu Chunxiao Han Yudan Zhao Haibo Li A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report BMC Medical Genomics IL7R Severe combined immunodeficiency Whole exome sequencing Chromosome microarray analysis Splicing variant |
| title | A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report |
| title_full | A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report |
| title_fullStr | A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report |
| title_full_unstemmed | A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report |
| title_short | A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report |
| title_sort | novel 268 kb deletion combined with a splicing variant in il7r causes of severe combined immunodeficiency in a chinese family a case report |
| topic | IL7R Severe combined immunodeficiency Whole exome sequencing Chromosome microarray analysis Splicing variant |
| url | https://doi.org/10.1186/s12920-023-01765-8 |
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