Submission Details

• Ras homolog family member H (RHOH) was first identified in Dallery et al in 1995 (PMID 7784061). Variant in RHOH was first reported in patients in 2012 (Crequer A, et al., 2012, PMID: 22850876). RHOH is a gene encoding for an atypical Rho GTPase specific for hematopoietic cells (PMID: 30156265). Canonical Rho GTPases function as intracellular switches, transducing signals from various membrane receptors, including T and B cell receptors. Atypical Rho GTPases, including RHOH, lack GTPase activity and therefore remain in the active, GTP-bound conformation(PMID: 22850876). One nonsense variant has been reported in 1 proband in 1 publication (PMIDs: 22850876). Affected individuals present persistent EV-HPV infections in early ages, naïve T cell lymphopenia. Patients’ T cells in PBMCs failed to proliferate in response to anti-CD3 stimulation, but showed weak proliferation to anti-CD3 plus anti-CD28 Ab, PHA, or PMA/ionomycin. Moreover, although RHOH is normally expressed in all leukocytes, the T cell lymphopenia is clearly the strongest phenotype in mice and human lacking RHOH (PMID: 17028588). Bone marrow cells from Rhoh–/– mice transduced with WT RHOH cDNA has significantly larger numbers of T cells, resulting in the partial rescue of Rhoh–/– T cell lymphopenia. In summary, RHOH is moderately associated with autosomal recessive RHOH deficiency. This has been demonstrated in both the research and the clinical diagnostic setting, but is not upheld over time because no more clinical diagnostic reported to date. Due to very limited genetic evidence, the classification is Limited. Classification approved by SCID-CID GCEP on Feb 17, 2023.