Disorders of immune dysregulation
Gene: SH2B3
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
2x unrelated patients with haematopoietic manifestations with predominantly myeloproliferative features. Both patients developed clinically significant extra‐haematopoietic multi‐organ autoimmune manifestations throughout life including autoimmune hypothyroidism, autoimmune hepatitis, alopecia areata and autoimmune diabetes mellitus.
Sources: LiteratureCreated: 26 Jul 2024, 3:43 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Immune
Publications
PMID:37206266
2x families
- hom missense variant Val402Met:
functional performed on patient's fibroblasts demonstrated increased basal pSTAT5, pSTAT3 and increased pJAK2 + pSTAT5 after stimulation with IL-3, GH, GM-CSF and EPO
- hom fs Arg148Profs*40
functional performed in zebrafish demonstrated increased number of macrophages and thrombocytes
PMID:23908464;
1 fam with 2 affecteds with dev delay + autoimmunity + (1x) ALL, hom for Asp231Gly fs*3
PMID:38152053;
JMML cohort - 2x hom missense + 2x het PTCsCreated: 1 Feb 2024, 12:29 a.m. | Last Modified: 1 Feb 2024, 12:29 a.m.
Panel Version: 1.1502
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: sh2b3 has been classified as Green List (High Evidence).
Phenotypes for gene: SH2B3 were changed from Immune to Predisposition to haematological malignancies; Myeloproliferation and multi-organ autoimmunity; juvenile myelomonocytic leukemia MONDO:001190, SH2B3-related
Gene: sh2b3 has been classified as Green List (High Evidence).
gene: SH2B3 was added gene: SH2B3 was added to Disorders of immune dysregulation. Sources: Literature Mode of inheritance for gene: SH2B3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SH2B3 were set to PMID: 37206266 Phenotypes for gene: SH2B3 were set to Immune Review for gene: SH2B3 was set to GREEN