This review article provides a detailed description of specific liver diseases occurring in various inborn errors of immunity. Awareness of these hepatobiliary diseases has lagged the improved management of the underlying disorders, leading to missed opportunities to improve clinical outcomes. A large spectrum of hepatobiliary diseases now present in those with immunodeficiency diseases, leading to morbidity and mortality in this population. As advancements in diagnosis through genetic testing and treatment with targeted immunotherapy and bone marrow transplant emerge, increasing numbers of patients survive into adulthood posing fresh clinical challenges. Inborn errors of immunity (IEIs) comprise numerous rare, inherited defects of the immune system that affect about 500,000 people in the United States. Ultimately, a healthy girl who had not carried disease-causing variants of SCID-X1 confirmed by prenatal diagnosis was born, further verifying our successful application of PGT in preventing mutated allele transmission for this SCID family. Prenatal genetic diagnosis was used to detect amniotic fluid cells, showing that this fetus did not carry the variant of the IL2RG gene (c.315T > A). Embryo E02 (ranking 4BB) has been transferred after considering the embryo growth rate, morphology, and PGT results. Four embryos (E02, E09, E10, and E11) were confirmed without CNVs and inherited variants at the IL2RG gene. After PGT for monogenic disorder, we detected the aneuploidy and copy number variation (CNV) for normal and female carrier embryos. In this case, Sanger sequencing for mutated allele and linkage analysis based on single-nucleotide polymorphism (SNP) haplotype via next-generation sequencing were performed simultaneously. This family gave birth to a boy who was a hemizygous proband whose IL2RG gene was mutated (c.315T > A, p(Tyr105*), NM_000206.3, CM962677). SCID-X1 is an X-linked recessive inherited disease whose major clinical manifestation of immune deficiency is the significant reduction in the number of T-cells and natural killer cells. In this study, we report a case where PGT was used to prevent the transmission of disease-caused variant in a SCID-X1 (OMIM:300400) family. Preimplantation genetic testing (PGT) has been increasingly used to prevent rare inherited diseases. This review is the updated, extended and largely modified translation of the article "Cossu F: Le basi genetiche delle SCID", originally published in Italian language in the journal "Prospettive in Pediatria" 2009, 156:228-238. Distinct forms of SCID show both common and peculiar (e.g., absence or presence of nonimmunological features) aspects, and they are currently classified into six groups according to prevalent pathophysiological mechanisms: impaired cytokine-mediated signaling pre-T cell receptor defects increased lymphocyte apoptosis defects in thymus embryogenesis impaired calcium flux other mechanisms. Over the last years novel genetic defects causing SCID have been discovered, and the molecular and immunological mechanisms of SCID have been better characterized. The knowledge of the genetic basis of SCID is essential for diagnosis (e.g., clinical phenotype, lymphocyte profile) and treatment (e.g., use and type of pre-hematopoietic stem cell transplant conditioning). Human SCID (Severe Combined Immunodeficiency) is a prenatal disorder of T lymphocyte development, that depends on the expression of numerous genes.
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