Objective: To report a new mutation in the YY1 gene in a patient with Gabriele-de Vries syndrome, in which dystonia and choreoathetosis were the most notable movement disorders.

Background: Gabriele-de Vries syndrome (MIM # 617557) is an autosomal dominant disorder, characterized by intellectual disability, dysmorphic facial features, and anomalies involving the eyes, heart, kidney, genitals, skeleton and CNS. Dystonia has been described in patients with this ultra-rare disease. Diagnosis of this disease is difficult, and it requires the use of next-generation sequencing (NGS) techniques, covering all diseases with intellectual disability, including the YY1 gene located on chromosome 14.

Method: The patient is a 49-year-old woman from southern Spain, who was being monitored in the Cerebral Palsy Unit due to her psychomotor delay. Starting at 38 years old, she developed a progressive profile involving cranio-cervical dystonia, gait disorder, choreoathetosis and tremor affecting the upper limbs. NGS was performed using the XGen Exome Panel kit v1.0 (IDT)

Results: NGS Assay with Sanger sequencing revealed a pathogenic YY1 de novo heterozygous frameshift deletion, c.1106_1114del; p.N369_R371del. This change is located on the third of the four C2H2-type zinc fingers located in the C-terminal of the protein. This variant is not reported in the Genome Aggregation Database (gnomAD) [https://gnomad.broadinstitute.org].

Conclusion: We identified a novel variant in the C-terminal domain of the YY1 protein in a patient with intellectual disability, in whom dystonia and choreoathetosis were the most prominent movement disorders. NGS may be useful in cases of suspected Combined Dystonia.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-new-mutation-in-the-c-terminal-domain-of-the-yy1-gene-associated-with-gabriele-de-vries-syndrome/