Clinical and Genetic Characteristics of Global Cohort of 132 Individuals with Janus Kinase-3 Deficiency

• DOI: 10.70962/cis2025abstract.169
• Publication Date: 2025-04-25T20:18:21Z
• Authors: Ekaterina Polyakova; Malgorzata Pac; Nel Dąbrowska-Leonik; Samaneh Delavari; Nima Rezaei; Hassan Abolhassani; Tinatin Tkemaladze; Oleg Kvilividze; Olga Pashchenko; Svetlana Vakhlyar...; Irina Kondratenko; Inga Sakovich; Irina Guryanova; Mikhail Belevtsev; Dmitry Tsekhanovich; Svetlana Aleshkevich; Vera Goda; Christoph Geier; Alexander Leiss-P...; Çiğdem Aydoğmuş; Pınar Gökmirza Öz...; Al Serdar; Rahim Miller; Ayca Kiykim; Safa Baris; Luigi Notarangelo; Andrew Gennery; Jolan Walter; Svetlana Sharapova

Background and Aims Janus kinase-3 (JAK3) deficiency, first described in 1995, is an autosomal recessive inborn error of immunity that mostly results variants severe combined immunodeficiency (SCID). The frequency estimated to account for 7-14% heritable SCID, with sporadic cases the Western world. Neither preferential “hot spots” nor founder effects have yet been documented. Hereby, we aim describe global experience JAK3-related diseases regarding clinical spectrum, genetic landscape, including treatment strategies. Methods We extracted clinical, genetic, immunological data from published on patients СID/SCID phenotype caused by defects JAK3 gene. literature search included unpublished collaborators, reports meetings European Society Immunodeficiencies (ESID), Clinical Immunology (CIS), biomedical research engine (PubMed) 1995 2024. Results Our cohort includes 132 47 unique defects, 35 novel (18 homozygous, 17 heterozygous). were 5 continents majority Asian ancestry. Country diagnosis North America (USA [n = 42]); South (Brazil 3]); Europe (Turkey 8], Hungary 1], Poland 6], UK 5], Italy Israel 4], Belarus Russian Federation 3], Georgia Spain Germany 1]); Asia (India 16], Iran 6],China Pakistan Japan Africa (Egypt Saudi Arabia Sudan 1]). Forty-five (35%) born consanguineous parents 31 families (n 3, 1-family), 3/2-family), 1), Turkey 8, 5-family), 4, 2-family), India Egypt(n 13, 8-family), 5, 4-family), China Brazil 1). 13 are identified. same variant was seen several countries. homozygous (68%); 40/132 compound heterozygous, 2 had germline heterozygous gain-of-function. occurred across entire gene no hotspots. Only 6 (5%) developed Omenn syndrome. 61 transplanted, died at age 9 months (mean 9-18 months), 44 alive. Conclusions time a subgroup. Patients identified four but most common countries high rate consanguinity. Founder effect 14 regions.