Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature
Abstract Background Defective Cernunnos gene in nonhomologous end‐joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular fe...
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
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| Online Access: | https://doi.org/10.1002/mgg3.1990 |
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| author | Mahnaz Jamee Nasrin Khakbazan Fard Shahrzad Fallah Zahra Golchehre Mazdak Fallahi Bibi Shahin Shamsian Samin Sharafian Zahra Chavoshzadeh |
| author_facet | Mahnaz Jamee Nasrin Khakbazan Fard Shahrzad Fallah Zahra Golchehre Mazdak Fallahi Bibi Shahin Shamsian Samin Sharafian Zahra Chavoshzadeh |
| author_sort | Mahnaz Jamee |
| collection | DOAJ |
| description | Abstract Background Defective Cernunnos gene in nonhomologous end‐joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular features of reported patients in the literature. Case The patient was a 6‐month‐old female born to consanguineous parents. She presented with long‐lasting fever, diarrhea, poor feeding, and restlessness. She had suffered from recurrent fever of unknown origin and multiple episodes of oral candidiasis. In the physical examination, microcephaly, failure to thrive, oral candidiasis, pustular rash on fingers, and perianal ulcers, but no dysmorphic feature were observed. The immunologic workup revealed lymphopenia, neutropenia, normocytic anemia, low T‐ but normal B‐ and natural killer (NK)‐ cells, low immunoglobulin (Ig)G, and normal IgA, IgM, and IgE. The T‐cell receptor excision circle (TREC) was low and the lymphocyte transformation test (LTT) was abnormal to mitogens and antigens. She was diagnosed with T− B+ NK+ SCID and improved by intravenous immunoglobulin along with antimicrobials. A homozygous splice site variant, c.390 + 1G > T, at the intron 3 of the NHEJ1, was identified and the diagnosis of Cernunnos deficiency was established. However, while a candidate for hematopoietic stem cell transplantation, she developed sepsis and died at 11 months of age. Conclusions Cernunnos deficiency should be considered as a differential diagnosis in patients with microcephaly, growth retardation, recurrent infections, T‐cell defects, and hypogammaglobulinemia. The normal B‐cell level in the index patient is an unexpected finding in Cernunnos deficiency which requires further evaluation. |
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| format | Article |
| id | doaj.art-12eeb2910f4a4f62a30754d098a71b78 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-12T07:26:41Z |
| publishDate | 2022-08-01 |
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| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-12eeb2910f4a4f62a30754d098a71b782022-12-22T03:42:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692022-08-01108n/an/a10.1002/mgg3.1990Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literatureMahnaz Jamee0Nasrin Khakbazan Fard1Shahrzad Fallah2Zahra Golchehre3Mazdak Fallahi4Bibi Shahin Shamsian5Samin Sharafian6Zahra Chavoshzadeh7Pediatric Nephrology Research Center Research Institute for Children’s Health Shahid Beheshti University of Medical Sciences Tehran IranImmunology and Allergy Department Mofid Children's Hospital Shahid Beheshti University of Medical Sciences Tehran IranImmunology and Allergy Department Mofid Children's Hospital Shahid Beheshti University of Medical Sciences Tehran IranDepartment of Medical Genetics School of Medicine Tehran University of Medical Sciences Tehran IranImmunology and Allergy Department Mofid Children's Hospital Shahid Beheshti University of Medical Sciences Tehran IranPediatric Congenital Hematologic Disorders Research Center Research Institute for Children’s Health Shahid Beheshti University of Medical Sciences Tehran IranImmunology and Allergy Department Mofid Children's Hospital Shahid Beheshti University of Medical Sciences Tehran IranImmunology and Allergy Department Mofid Children's Hospital Shahid Beheshti University of Medical Sciences Tehran IranAbstract Background Defective Cernunnos gene in nonhomologous end‐joining (NHEJ) pathway of the DNA repair is responsible for radiosensitive severe combined immunodeficiency (SCID). Herein, presented a new patient with Cernunnos deficiency and summarized the clinical, immunological, and molecular features of reported patients in the literature. Case The patient was a 6‐month‐old female born to consanguineous parents. She presented with long‐lasting fever, diarrhea, poor feeding, and restlessness. She had suffered from recurrent fever of unknown origin and multiple episodes of oral candidiasis. In the physical examination, microcephaly, failure to thrive, oral candidiasis, pustular rash on fingers, and perianal ulcers, but no dysmorphic feature were observed. The immunologic workup revealed lymphopenia, neutropenia, normocytic anemia, low T‐ but normal B‐ and natural killer (NK)‐ cells, low immunoglobulin (Ig)G, and normal IgA, IgM, and IgE. The T‐cell receptor excision circle (TREC) was low and the lymphocyte transformation test (LTT) was abnormal to mitogens and antigens. She was diagnosed with T− B+ NK+ SCID and improved by intravenous immunoglobulin along with antimicrobials. A homozygous splice site variant, c.390 + 1G > T, at the intron 3 of the NHEJ1, was identified and the diagnosis of Cernunnos deficiency was established. However, while a candidate for hematopoietic stem cell transplantation, she developed sepsis and died at 11 months of age. Conclusions Cernunnos deficiency should be considered as a differential diagnosis in patients with microcephaly, growth retardation, recurrent infections, T‐cell defects, and hypogammaglobulinemia. The normal B‐cell level in the index patient is an unexpected finding in Cernunnos deficiency which requires further evaluation.https://doi.org/10.1002/mgg3.1990BCGCernunnos deficiencyinborn errors of immunityNHEJ1SCIDsevere combined immunodeficiency |
| spellingShingle | Mahnaz Jamee Nasrin Khakbazan Fard Shahrzad Fallah Zahra Golchehre Mazdak Fallahi Bibi Shahin Shamsian Samin Sharafian Zahra Chavoshzadeh Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature Molecular Genetics & Genomic Medicine BCG Cernunnos deficiency inborn errors of immunity NHEJ1 SCID severe combined immunodeficiency |
| title | Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature |
| title_full | Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature |
| title_fullStr | Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature |
| title_full_unstemmed | Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature |
| title_short | Cernunnos defect in an Iranian patient with T− B+ NK+ severe combined immunodeficiency: A case report and review of the literature |
| title_sort | cernunnos defect in an iranian patient with t b nk severe combined immunodeficiency a case report and review of the literature |
| topic | BCG Cernunnos deficiency inborn errors of immunity NHEJ1 SCID severe combined immunodeficiency |
| url | https://doi.org/10.1002/mgg3.1990 |
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