Aims: to expand and refine the clinical and molecular spectrum of ZNF462-related Weiss-Kruszka syndrome, to establish more robust feature frequencies and any genotype-phenotype relationships across a larger international cohort, and to correlate the emerging chromatin-based disease mechanism with the human phenotype.
Inclusion criteria: individuals of any age with a heterozygous pathogenic or likely pathogenic ZNF462variant, a contiguous 9q31.2 deletion involving ZNF462, or a structural rearrangement disrupting ZNF462, confirmed on clinical genomic testing.
Methods:standardised deep phenotyping (including HPO coding), collection of facial images for next-generation facial-analysis (for example GestaltMatcher), central collation of variant data, and, where consent permits, functional follow-up of variants of uncertain significance. Data sharing through the Human Disease Genes website patient forms and, where appropriate, GeneMatcher and Simons Searchlight.
Expected results: a larger, more precisely characterised cohort that clarifies natural history (including in adults), sharpens diagnostic recognition, and informs anticipatory management and genetic counselling. Moderators welcome contact from clinicians and researchers with additional cases or collaborative proposals.
ZNF462