Clinical and genetic spectrum of RHOBTB2-related disorders: A study integrating Chinese and international cohorts for genotype-phenotype correlations and clinical subtyping.

De novo missense variants in RHOBTB2, mostly in the BTB domain (hotspot p.Arg483His).

Characterisation of the clinical and genetic spectrum of RHOBTB2-related disorders integrating 12 Chinese patients and 79 international cases (N = 91). In the Chinese cohort, all variants were de novo missense, 75 % in the BTB domain and at conserved hotspots (p.Arg483His). The authors propose, as an exploratory step, a new phenotypic cluster — paroxysmal encephalopathy with weakness (PEW) — strongly associated with BTB-domain variants, and a practical subtyping framework (BTB, truncating/splicing, GTPase and interdomain subtypes). This framework aims to improve diagnostic accuracy and guide management.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value is the genotype-phenotype subtyping framework, potentially useful for anticipating severity (BTB variants being more severe) and guiding seizure management. The PEW cluster remains exploratory and needs replication. It confirms conserved hotspots across populations, which supports interpretation of RHOBTB2 variants.

Analysis by Dr Thibaut Benquey