ABSTRACT
Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive degeneration of the central nervous system and high basal ganglia iron deposition. The list of identified causative genes for NBIA syndromes continues to expand and includes one autosomal dominant, one X-linked, and a number of recessive forms. Mitochondrial membrane protein-associated neurodegeneration is a recently described NBIA syndrome caused by C19orf12 mutations. In this study, we report two consanguineous families with a homozygous C19orf12 p.Thr11Met mutation. Our patients presented at a later age and had more rapid disease progression, leading to early death in two, than those previously reported. We conclude that C19orf12 mutation is associated with wide phenotypic heterogeneity, and that further research is needed to examine the role of C19orf12 in NBIA and related diseases and to elucidate its protein function as well as other factors that may affect disease progression and expression.
