Andrey Marakhonov, Elena Serebryakova, Anna Mukhina, Anastasia Vechkasova, Nikolai Prokhorov, Irina Efimova, Natalia Balinova, Anastasia Lobenskaya, Tatyana Vasilyeva, Victoria Zabnenkova, Oxana Ryzhkova, Yulia Rodina, Dmitry Pershin, Nadezhda Soloveva, Anna Fomenko, Djamila Saydaeva, Aset Ibisheva, Taisiya Irbaieva, Alexander Koroteev, Rena Zinchenko, Sergey Voronin, Anna Shcherbina, Sergey Kutsev
{"title":"利用 TREC 进行新生儿筛查发现一例罕见的 TP63 相关淋巴细胞减少症病例","authors":"Andrey Marakhonov, Elena Serebryakova, Anna Mukhina, Anastasia Vechkasova, Nikolai Prokhorov, Irina Efimova, Natalia Balinova, Anastasia Lobenskaya, Tatyana Vasilyeva, Victoria Zabnenkova, Oxana Ryzhkova, Yulia Rodina, Dmitry Pershin, Nadezhda Soloveva, Anna Fomenko, Djamila Saydaeva, Aset Ibisheva, Taisiya Irbaieva, Alexander Koroteev, Rena Zinchenko, Sergey Voronin, Anna Shcherbina, Sergey Kutsev","doi":"10.3390/ijms251910844","DOIUrl":null,"url":null,"abstract":"<p><p>The expanded newborn screening (NBS) program in the Russian Federation was initiated in 2023, among which severe combined immunodeficiency (SCID) is screened using TREC/KREC assays. Here, we report a rare case of a <i>TP63</i>-associated disease identified through this NBS program. Dried blood spots from newborns were initially screened for TREC/KREC levels, and those with values below the cut-off underwent confirmatory testing and further genetic analysis, including whole-exome sequencing (WES). A male newborn was identified with significantly reduced TREC values, indicative of T cell lymphopenia. Genetic analysis revealed a heterozygous NM_003722.5:c.1027C>T variant in <i>TP63</i>, leading to the p.(Arg343Trp) substitution within the DNA binding domain. This mutation has been previously associated with Ectrodactyly-Ectodermal Dysplasia-Cleft lip/palate syndrome (EEC) syndrome and shown to reduce the transactivation activity of TP63 in a dominant-negative manner. This case represents one of the few instances of immune system involvement in a patient with a <i>TP63</i> mutation, highlighting the need for further investigation into the immunological aspects of <i>TP63</i>-associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with <i>TP63</i> mutations to better understand and manage potential immune dysfunctions.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":5.6000,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482481/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Rare Case of <i>TP63</i>-Associated Lymphopenia Revealed by Newborn Screening Using TREC.\",\"authors\":\"Andrey Marakhonov, Elena Serebryakova, Anna Mukhina, Anastasia Vechkasova, Nikolai Prokhorov, Irina Efimova, Natalia Balinova, Anastasia Lobenskaya, Tatyana Vasilyeva, Victoria Zabnenkova, Oxana Ryzhkova, Yulia Rodina, Dmitry Pershin, Nadezhda Soloveva, Anna Fomenko, Djamila Saydaeva, Aset Ibisheva, Taisiya Irbaieva, Alexander Koroteev, Rena Zinchenko, Sergey Voronin, Anna Shcherbina, Sergey Kutsev\",\"doi\":\"10.3390/ijms251910844\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The expanded newborn screening (NBS) program in the Russian Federation was initiated in 2023, among which severe combined immunodeficiency (SCID) is screened using TREC/KREC assays. Here, we report a rare case of a <i>TP63</i>-associated disease identified through this NBS program. Dried blood spots from newborns were initially screened for TREC/KREC levels, and those with values below the cut-off underwent confirmatory testing and further genetic analysis, including whole-exome sequencing (WES). A male newborn was identified with significantly reduced TREC values, indicative of T cell lymphopenia. Genetic analysis revealed a heterozygous NM_003722.5:c.1027C>T variant in <i>TP63</i>, leading to the p.(Arg343Trp) substitution within the DNA binding domain. This mutation has been previously associated with Ectrodactyly-Ectodermal Dysplasia-Cleft lip/palate syndrome (EEC) syndrome and shown to reduce the transactivation activity of TP63 in a dominant-negative manner. This case represents one of the few instances of immune system involvement in a patient with a <i>TP63</i> mutation, highlighting the need for further investigation into the immunological aspects of <i>TP63</i>-associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with <i>TP63</i> mutations to better understand and manage potential immune dysfunctions.</p>\",\"PeriodicalId\":14156,\"journal\":{\"name\":\"International Journal of Molecular Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2024-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482481/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Molecular Sciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/ijms251910844\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Molecular Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/ijms251910844","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
A Rare Case of TP63-Associated Lymphopenia Revealed by Newborn Screening Using TREC.
The expanded newborn screening (NBS) program in the Russian Federation was initiated in 2023, among which severe combined immunodeficiency (SCID) is screened using TREC/KREC assays. Here, we report a rare case of a TP63-associated disease identified through this NBS program. Dried blood spots from newborns were initially screened for TREC/KREC levels, and those with values below the cut-off underwent confirmatory testing and further genetic analysis, including whole-exome sequencing (WES). A male newborn was identified with significantly reduced TREC values, indicative of T cell lymphopenia. Genetic analysis revealed a heterozygous NM_003722.5:c.1027C>T variant in TP63, leading to the p.(Arg343Trp) substitution within the DNA binding domain. This mutation has been previously associated with Ectrodactyly-Ectodermal Dysplasia-Cleft lip/palate syndrome (EEC) syndrome and shown to reduce the transactivation activity of TP63 in a dominant-negative manner. This case represents one of the few instances of immune system involvement in a patient with a TP63 mutation, highlighting the need for further investigation into the immunological aspects of TP63-associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with TP63 mutations to better understand and manage potential immune dysfunctions.
期刊介绍:
The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).