A Rare Case of TP63 -Associated Lymphopenia Revealed by Newborn Screening Using TREC

• Published in: International journal of molecular sciences Vol. 25; no. 19; p. 10844
• Main Authors: Marakhonov, Andrey, Serebryakova, Elena, Mukhina, Anna, Vechkasova, Anastasia, Prokhorov, Nikolai, Efimova, Irina, Balinova, Natalia, Lobenskaya, Anastasia, Vasilyeva, Tatyana, Zabnenkova, Victoria, Ryzhkova, Oxana, Rodina, Yulia, Pershin, Dmitry, Soloveva, Nadezhda, Fomenko, Anna, Saydaeva, Djamila, Ibisheva, Aset, Irbaieva, Taisiya, Koroteev, Alexander, Zinchenko, Rena, Voronin, Sergey, Shcherbina, Anna, Kutsev, Sergey
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.10.2024; MDPI
• Subjects: Apoptosis; Birth defects; Case Report; Cells; Circular DNA; Congenital diseases; Diagnosis; ectodermal dysplasia; ectrodactyly; Exome Sequencing; Genes; Genetic aspects; Genetic testing; Genomes; Health aspects; Humans; Immune system; Infant, Newborn; Infants (Newborn); KREC; Lymphocytes; Lymphocytopenia; lymphopenia; Lymphopenia - diagnosis; Lymphopenia - genetics; Male; Medical examination; Medical screening; Mutation; Neonatal Screening; newborn screening; Pediatric research; Proteins; Severe Combined Immunodeficiency - diagnosis; Severe Combined Immunodeficiency - genetics; Thymus gland; Transcription factors; Transcription Factors - genetics; TREC; Tumor Suppressor Proteins - genetics; Urogenital system; Russia; ectodermal dysplasia; KREC; cleft-lip/palate; TREC; ectrodactyly; newborn screening; TP63; lymphopenia
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms251910844

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 -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 , 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 mutation, highlighting the need for further investigation into the immunological aspects of -associated disorders. Our findings suggest that comprehensive immunological evaluation should be considered for patients with mutations to better understand and manage potential immune dysfunctions.