Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| HUSP Clinical Genetics Laboratory, |
RCV004557276 | SCV005046456 | likely pathogenic | Autosomal dominant intellectual disability-craniofacial anomalies-cardiac defects syndrome | criteria provided, single submitter | clinical testing | The variant was detected in a 17-years-old woman with development delay, autism spectrum disorder, subclinical hypothyroidism and seizures. He presented the variant c.3887dupC in exon 17 of KAT6A in heterozygosity (NM_006766.5). It results in a frameshift, a premature termination codon and, therefore, a truncated protein (p.Glu1297ArgfsTer16). This variant is not detected in general population and has not been reported in pathogenic data bases. A genetic study has been carried out in the parents and it is determined that none of them presents the variant, so it appears de novo in our patient. The loss of function of the protein predicted by in silico tools added to de-novo origin made us labeled the variant as pathogenic. Pathogenic variants in KAT6A have been associated with Arboleda-Tham syndrome (OMIM: 616268). This clinical entity is characterized by intellectual disability, speech delay, microcephaly, and gastrointestinal complications. Half of the patients present cardiac anomalies and strabismus and 25% of patients have been detected autism spectrum disorder. Variants described that results in truncated protein exons 16-17 are associated with moderate to severe intellectual disability while those located in exons 1-15 are associated with mild intellectual disability. The inheritance pattern is autosomal dominant. |