Clinical and Genetic Characteristics of Global Cohort of 132 Individuals with Janus Kinase-3 Deficiency
Notice bibliographique
Résumé
Background and Aims Janus kinase-3 (JAK3) deficiency, first described in 1995, is an autosomal recessive inborn error of immunity that mostly results in variants of severe combined immunodeficiency (SCID). The frequency is estimated to account for 7-14% of heritable SCID, with sporadic cases in the Western world. Neither preferential “hot spots” nor founder effects have yet been documented. Hereby, we aim to describe the global experience of JAK3-related diseases regarding clinical spectrum, genetic landscape, including founder variants and treatment strategies. Methods We extracted clinical, genetic, and immunological data from published cases on patients with СID/SCID phenotype caused by defects in the JAK3 gene. The literature search included unpublished cases from collaborators, reports from meetings of the European Society for Immunodeficiencies (ESID), of the Clinical Immunology Society (CIS), and published data in the biomedical research search engine (PubMed) from 1995 to 2024. Results Our cohort includes 132 patients with 47 unique genetic defects, including 35 novel variants (18 homozygous, 17 heterozygous). The patients were from 5 continents with majority of Asian ancestry. Country of diagnosis included North America (USA [n = 42]); South America (Brazil [n = 3]); Europe (Turkey [n = 8], Hungary [n = 1], Poland [n = 6], UK [n = 5], Italy [n = 5], Israel [n = 4], Belarus [n = 4], Russian Federation [n = 3], Georgia [n = 3], Spain [n = 1], Germany [n = 1]); Asia (India [n = 16], Iran [n = 6],China [n = 4], Pakistan [n = 1], Japan [n = 1]); and Africa (Egypt [n = 16], Saudi Arabia [n = 1], Sudan [n = 1]). Forty-five (35%) of patients from the cohort were born to consanguineous parents in 31 families from Georgia (n = 3, 1-family), Russian Federation (n = 3/2-family), Sudan (n = 1), Turkey (n = 8, 5-family), Israel (n = 4, 2-family), India (n = 3, 2-family), Egypt(n = 13, 8-family), UK (n = 5, 4-family), China (n = 1), Brazil (n = 1), Spain (n = 1), Italy (n = 1), Pakistan (n = 1), and Saudi (n = 1). 13 novel founder variants are identified. The same founder variant was seen in several countries. The majority of genetic defects were homozygous (68%); 40/132 compound were heterozygous, and 2 patients had germline heterozygous gain-of-function. The variants occurred across the entire JAK3 gene with no hotspots. Only 6 (5%) of 132 cases developed Omenn syndrome. 61 patients were transplanted, 17 died at the age of 9 months (mean age 9-18 months), and 44 are alive. Conclusions We describe for the first time a global cohort of JAK3 with 132 patients with founder effects in a subgroup. Patients were identified in four continents but are most common in countries with a high rate of consanguinity. Founder effect was identified in 14 regions.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».