Targeted gene(s)/phenotype under study :
BUD23 is a methyltransferase forming heterodimers with TMRT112 and involved in the maturation of the 18S ribosomal subunit. It is also commonly deleted in Williams-Beuren syndrome.
We found homozygous missense variants in a girl with progressive dystonia of childhood. Study of the patient’s fibroblasts (Denis Lafontaine) showed an accumulation of the 18S-E immature rRNA which demonstrates biological effects of the variant.
We are looking for other patients with a similar phenotype and biallelic variants in BUD23, expecting missense variants with strong predicted pathogenicity rather than truncating variants, which may be lethal.
One may also consider the possibility of missense variants in BUD23 in trans in patients with Williams-Beuren syndrome and unusual childhood-onset dystonia. Given that TRMT112 is a cofactor of BUD23, (biallelic) variants in this gene may have similar consequences. Thus, we also look for patients with such variants and progressive dystonia.
Coordinating clinicians /researchers: Dr Cyril Mignot
Institution: Dept of Genetics, Hôpital Trousseau, Groupe Hospitalier Pitié-Salpêtrière
Specific requirements beyond clinical data and genotype data sharing:
- Re-analysis of DNA samples: no
- Resampling of patients: no
- Linked to a translational/basic research project: yes, conducted by Marc Graille and Denis Lafontaine