BACKGROUND: Recently, mutations in an open-reading frame on chromosome 19 (C19orf12) were identified as a novel genetic factor in neurodegeneration with brain iron accumulation (NBIA). Because of the mitochondrial localization of the derived protein, this variant is referred to as mitochondrial membrane protein-associated neurodegeneration with brain iron accumulation (MPAN). METHODS/ RESULTS: We describe the clinical phenotype and MRI of 3 newly identified individuals with MPAN due to either previously reported or novel homozygous or compound heterozygous genetic alterations in C19orf12. CONCLUSIONS: MPAN is characterized by a juvenile-onset, slowly progressive phenotype with predominant lower limb spasticity, generalized dystonia, and cognitive impairment. Typical additional features include axonal motor neuropathy and atrophy of the optic nerve. MRI showed iron deposition in the globus pallidus and substantia nigra without the eye-of-the-tiger sign, which is typical for PKAN, the most frequent form of NBIA.
BACKGROUND: Recently, mutations in an open-reading frame on chromosome 19 (C19orf12) were identified as a novel genetic factor in neurodegeneration with brain iron accumulation (NBIA). Because of the mitochondrial localization of the derived protein, this variant is referred to as mitochondrial membrane protein-associated neurodegeneration with brain iron accumulation (MPAN). METHODS/ RESULTS: We describe the clinical phenotype and MRI of 3 newly identified individuals with MPAN due to either previously reported or novel homozygous or compound heterozygous genetic alterations in C19orf12. CONCLUSIONS: MPAN is characterized by a juvenile-onset, slowly progressive phenotype with predominant lower limb spasticity, generalized dystonia, and cognitive impairment. Typical additional features include axonal motor neuropathy and atrophy of the optic nerve. MRI showed iron deposition in the globus pallidus and substantia nigra without the eye-of-the-tiger sign, which is typical for PKAN, the most frequent form of NBIA.
Authors: Michaela Auer-Grumbach; Stefan Toegel; Maria Schabhüttl; Daniela Weinmann; Catharina Chiari; David L H Bennett; Christian Beetz; Dennis Klein; Peter M Andersen; Ilka Böhme; Regina Fink-Puches; Michael Gonzalez; Matthew B Harms; William Motley; Mary M Reilly; Wilfried Renner; Sabine Rudnik-Schöneborn; Beate Schlotter-Weigel; Andreas C Themistocleous; Jochen H Weishaupt; Albert C Ludolph; Thomas Wieland; Feifei Tao; Lisa Abreu; Reinhard Windhager; Manuela Zitzelsberger; Tim M Strom; Thomas Walther; Steven S Scherer; Stephan Züchner; Rudolf Martini; Jan Senderek Journal: Am J Hum Genet Date: 2016-09-01 Impact factor: 11.025
Authors: Ethan Gore; Brian S Appleby; Mark L Cohen; Suzanne D DeBrosse; James B Leverenz; Bruce L Miller; Sandra L Siedlak; Xiongwei Zhu; Alan J Lerner Journal: Neurocase Date: 2016-11-01 Impact factor: 0.881