Pantothenate kinase-associated neurodegeneration (PKAN): molecular confirmation of a Turkish patient with a rare frameshift mutation in the coding region of the PANK2 gene.

Here we report the clinical, neuroimaging, and molecular findings of a classic pantothenate kinase-associated neurodegeneration (PKAN) patient of Turkish origin. Our patient is the first reported case of PKAN in Turkey with molecular genetic confirmation of the diagnosis. The frameshift mutation c.821_822delCT of the PANK2 gene detected in our patient has only been described in such classic patients to date, and our case provides further evidence of the association of this mutation with the classic PKAN phenotype. Since this mutation is a rare disease-causing mutation in other populations, further studies of more Turkish PKAN patients will show if it is the result of a founder effect in this population. In our case, molecular diagnosis allowed accurate prenatal genetic testing and counseling for this family. This case report highlights the importance of magnetic resonance imaging and molecular investigation in children who have progressive neurodegenerative symptoms of parkinsonism, dystonia, pyramidal features, and dementia.

A distinct autosomal recessive ataxia maps to chromosome 12 in an inbred family from Jordan.

Autosomal recessive ataxias are a heterogeneous group of rare disorders characterized by early onset ataxia associated with neurologic, ophthalmologic or systemic signs. The ataxias associated with myoclonus, epilepsy and progressive neurological degeneration are usually included with the progressive myoclonus epilepsies, one of which is Unverricht-Lundborg disease. We identified four siblings with ataxia, juvenile onset progressive action tremor and atonic seizures from a Jordanian family. The mode of inheritance of this syndrome is autosomal recessive. We performed a genome-wide screen for linkage and fine mapped the region that contains the disease locus. The four affected siblings have ataxia noted at the onset of walking with dysarthria and bulbar features, but no cerebellar hypoplasia on MRI. They all developed a fine tremor that progressed to a coarse action tremor, as well as atonic seizures. Treatment with valproate fully controlled the seizures and improved the tremor, but did not change the course of the ataxia. We mapped the gene responsible for this disorder to the pericentromeric region of chromosome 12. A recently described autosomal recessive variant of Unverricht-Lundborg disease also maps to the same region. We discuss the similarities and differences between our family and the family with the Unverricht-Lundborg disease variant.