A new NBIA patient from Turkey with homozygous C19ORF12 mutation

Excerpt

Neurodegeneration with brain iron accumulation (NBIA) comprises a group of disorders with a progressive extrapyramidal syndrome and excessive iron deposition in the brain, particularly globus pallidus and substantia nigra. NBIA is considered to be a very rare disease group, with a prevalence of less than 1/1,000,000 in the general population [1‐3]. Ten genes have been identified as associated with different NBIA subtypes. Only two of these genes (FTL and CP) encode proteins that play a direct role in iron metabolism, while the remaining eight (PANK2, PLA2G6, C19orf12, WDR45, FA2H, ATP13A2, DCAF17, and COASY) encode proteins involved in lipid metabolism, mitochondrial function, coenzyme A (CoA) metabolism, and autophagy [4]. The most common forms of NBIA are pantothenate kinase-associated neurodegeneration (PKAN), PLA2G6-associated neurodegeneration (PLAN), and beta propeller protein-associated neurodegeneration (BPAN). Mitochondrial membrane protein-associated neurodegeneration (MPAN) occurs less frequently. It is inherited in an autosomal recessive fashion, and a common Polish mutation has been identified in several cases. MPAN is caused by biallelic mutations in C19orf12, which encodes a protein of the mitochondrial membrane [5, 6]. Herein, we present a patient with progressive neurocognitive decline after normal development during infancy, undiagnosed for 19 years until detailed genetic analysis revealed mutations in C19orf12. …