Disorders of immune dysregulation
Gene: DPP9
3 unrelated families and supporting null mouse model. IUIS IEI committee assign the condition to diseases of immune dysregulation in the subcategory of Familial Hemophagocytic Lymphohistiocytosis (FHL syndromes).
Sources: Expert ReviewCreated: 16 Nov 2024, 2:30 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
hatipoglu immunodeficiency syndrome MONDO:0957229
Publications
Variants in this GENE are reported as part of current diagnostic practice
Three families (four children) with immune-associated defects, poor growth, pancytopenia and skin pigmentation abnormalities that segregate with biallelic DPP9 rare variants.
Using patient-derived primary cells and biochemical assays, these variants were shown to behave as hylomorphic or knockout alleles that failed to repress NLRP1. Experiments suggested that the deleterious consequences of DPP9 deficiency were mostly driven by the aberrant activation of the canonical NLRP1 inflammasome.
Recessive loss of function DPP9 germline variants found in three families.
c.2551C>T; p.(Gln851*) homozygous in child and het in parents.
c.449G>A; p.(Gly167Ser)/c.641C>G; p.(Ser214*) comp het child, proven in trans.
c.331C>T; p.(Arg111*) homozygous in one child and two cousins (consanguineous family).
All four children shared a triad of symptoms which were termed “Hatipoglu syndrome”. These included failure to thrive, skin manifestations, pancytopenia and susceptibility to infections. This Mendelian disease bears some degree of resemblance with auto-immune disorders caused by NLRP1 activating mutations.Created: 4 May 2023, 2:26 a.m. | Last Modified: 4 May 2023, 2:26 a.m.
Panel Version: 1.4
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hatipoglu immunodeficiency syndrome MIM#620331
Publications
Amber for mono-allelic association:
de novo monoallelic dominant-negative mutation in DPP9 (c.755G>C, R252P) presenting with HLH at ~2m. Functional data supporting dominant negative mechanism.Created: 8 Aug 2023, 6:32 a.m. | Last Modified: 8 Aug 2023, 6:32 a.m.
Panel Version: 1.1095
Three unrelated families with Hatipoğlu syndrome with biochemical and cellular assays, mouse and zebrafish models. Immunological features of recurrent fevers, repeated infections, herpes susceptibility, cytopenias.
Sources: Expert ReviewCreated: 22 Sep 2022, 8:42 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Autoinflammatory syndrome MONDO:0019751, DPP9-related; recurrent fevers; repeated infections; herpes susceptibility; cytopenias
Publications
de novo monoallelic dominant-negative mutation in DPP9 (c.755G>C, R252P) presenting with HLH at ~2m. Functional data supporting dominant negative mechanism.Created: 7 Aug 2023, 11:39 p.m. | Last Modified: 7 Aug 2023, 11:39 p.m.
Panel Version: 1.9
Three unrelated families with Hatipoğlu syndrome with biochemical and cellular assays, mouse and zebrafish models. Immunological features of recurrent fevers, repeated infections, herpes susceptibility, cytopaenias.
Sources: LiteratureCreated: 19 Sep 2022, 10 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
HLH
Publications
Gene: dpp9 has been classified as Green List (High Evidence).
Gene: dpp9 has been classified as Green List (High Evidence).
gene: DPP9 was added gene: DPP9 was added to Disorders of immune dysregulation. Sources: Expert Review Mode of inheritance for gene: DPP9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: DPP9 were set to 36112693 Phenotypes for gene: DPP9 were set to hatipoglu immunodeficiency syndrome MONDO:0957229 Review for gene: DPP9 was set to GREEN gene: DPP9 was marked as current diagnostic