Browsing by Author "Chinn, Ivan"

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    Clinical, immunologic, and genetic characteristics of 148 patients with natural killer cell deficiency
    (2025) Abdalgani, Manar; Hernandez , Evelyn; Pedroza, Luis; Chinn, Ivan; Forbes, Lisa; Rider, Nicholas; Banerjee, Pinaki; Poli Harlowe, María Cecilia; Mahapatra, Sanjana; Canter, Debra; Cao, Tram; Shawver, Linda; Nandiwada, Sarada; Lupski, James; Posey, Jennifer; Ramakrishnan, Rajasekhar; Mace, Emily; Orange, Jordan
    Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect. Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice. Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations. Results: NK cell abnormalities consistent with NKD were confirmed in 148 participants. Most presented during childhood (median age 13 years, range 0-76 years), though 34% were adults. All tested individuals exhibited reduced NK cell cytotoxic function; 44% also had decreased NK cell numbers and/or mature NK cells. Herpesvirus and/or papillomavirus infections were observed in 71%, malignancies were observed in 7%, and a 5% case-fatality rate was noted. Among the 99 participants who underwent research exome sequencing, 29% were considered solved for a likely contributing variant allele, with 52% of these cases involving known genes and 48% involving novel genes. Conclusions: NKD is a phenotypic immunodeficiency associated with increased susceptibility to certain viral infections and cancer with multiple genetic etiologies, revealing key biological pathways for NK cell development and function. This research underscores the role of NK cells in human immune defenses and helps advance the identification of at-risk populations, precise genetic diagnoses, and informed clinical management for patients with NKD.
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    Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. Case Series and Review of the Literature.
    (Frontiers, 2019) Staines, Aidé; Chinn, Ivan; Alaez-Versón, Carmen; Yamazaki-Nakashimada, Marco; Carrillo-Sánchez, Karol; García-Cruz, María de la Luz; Poli, Cecilia; González Serrano, Edith; Medina, Edgar; Muzquiz, David; Forbes, Lisa; Espinosa-Rosales, Francisco; Espinosa-Padilla, Sara; Orange, Jordan; Lugo, Saul
    DNA repair defects are inborn errors of immunity that result in increased apoptosis and oncogenesis. DNA Ligase 4-deficient patients suffer from a wide range of clinical manifestations since early in life, including: microcephaly, dysmorphic facial features, growth failure, developmental delay, mental retardation; hip dysplasia, and other skeletal malformations; as well as a severe combined immunodeficiency, radiosensitivity, and progressive bone marrow failure; or, they may present later in life with hematological neoplasias that respond catastrophically to chemo- and radiotherapy; or, they could be asymptomatic. We describe the clinical, laboratory, and genetic features of five Mexican patients with LIG4 deficiency, together with a review of 36 other patients available in PubMed Medline. Four out of five of our patients are dead from lymphoma or bone marrow failure, with severe infection and massive bleeding; the fifth patient is asymptomatic despite a persistent CD4+ lymphopenia. Most patients reported in the literature are microcephalic females with growth failure, sinopulmonary infections, hypogammaglobulinemia, very low B-cells, and radiosensitivity; while bone marrow failure and malignancy may develop at a later age. Dysmorphic facial features, congenital hip dysplasia, chronic liver disease, gradual pancytopenia, lymphoma or leukemia, thrombocytopenia, and gastrointestinal bleeding have been reported as well. Most mutations are compound heterozygous, and all of them are hypomorphic, with two common truncating mutations accounting for the majority of patients. Stem-cell transplantation after reduced intensity conditioning regimes may be curative.
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    Partial loss-of-function mutations in GINS4 lead to NK cell deficiency with neutropenia
    (2022) Conte, Matilde; Poli, Cecilia; Taglialatela, Angelo; Leuzzi, Giuseppe; Chinn, Ivan; Salinas, Sandra; Rey, Emma; Olivares, Nixa; Veramendi, Liz; Ciccia, Alberto; Lupsk, James; Orange, Jordan; Aldave, Juan; Mace, Emily

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