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    Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy
    2
    1. ClingenBaseline 23 Oct 2026
      a single base deletion (c.G222del) in exon 2 led to a frame-shift terminating the protein at position 74 of 412 amino acids

      Case 18-IV-1

      Proband? Yes

      Phenotype HPOs: HP:0001249, HP:0000708, HP:0008762, HP:0002373, HP:0002197, HP:0010892, HP:0000729

      HPOFreeText: Failure to meet developmental milestones: did not sit until one year, never crawled, began to walk at two years, said her first words at two years old and never spoke in sentences.

      NotHPOs: HP:0001507

      Demographics: Female, Turkey, 21yrs (at report - final age)

      Previous Testing? The proband tested negative for known metabolic disorders. additionally, no chromosomal abnormalities were identified and cranial MRI was normal.

      Genotyping Method:

      Variant Info:

      Variant: c.222del (p.Met74IlefsTer15)

      CAID:CA891862642 ID created for this curation

      gnomAD: Found. Highest MAF 0.00003249 (South Asia), No homozygotes (all populations)

      Variant Evidence: Authors show reduced BCKDK mRNA levels and undetectable BCKDK protein levels in patient derived fibroblasts, suggesting nonsense-mediated decay.

      Additional Case Info: Family described to be of Egyptian ancestry. Parental first-cousin consanguinity. Had one sibling who was similarly affected. Allele Registry CAID created for this curation.

      Other Reporting PMIDs:

      Case Variant inferred_gene_hgnc:16902 inferred_gene_source:CAID ClinGen Aminoacidopathy
    2. ClingenBaseline 23 Oct 2026
      Relative to controls, we found reduced mRNA levels in cell lines from the two affected patients in families 558 and 18, suggesting nonsense-mediated mRNA decay (Fig. 2A and fig. S3A), as well as undetectable levels of BCKDK protein on Western blot (Fig. 2B and fig. S3B).

      Likely Variant Evidence for Variant: c.466C>T (p.Arg156Ter) ClinVar: 39743 and Variant:c.222del (p.Met74IlefsTer15) CAID: CA891862642

      VariantEvidence inferred_gene_hgnc:16902 inferred_gene_source:CAID ClinGen Aminoacidopathy
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    ncbi.nlm.nih.gov/pmc/articles/PMC3704165/