Objective:

To genetically and clinically characterize a series of Turkish patients affected by neurodegeneration with brain iron accumulation (NBIA) compatible with an autosomal recessive form of inheritance.

Background: Mitochondrial-membrane protein associated neurodegeneration (MPAN) is an autosomal recessive form of NBIA caused by mutations in C19orf12 gene. A limited number of patients, particularly those with an adult onset of symptoms, have been reported with C19orf12 mutations.

Methods: We sequenced the entire C19orf12 coding region in 15 Turkish adult probands with idiopathic NBIA. We also performed haplotype analysis in families with a recurrent C19orf12 mutation. Clinical features were collected using a standardized form.

Results:

Nine of our 15 probands (60%) carried the homozygous c.32C>T mutation in C19orf12 (predicted protein effect: p.Thr11Met). This homozygous mutation co-segregated with the disease in all affected relatives available for testing (total of 16 homozygous subjects). Haplotypes across the C19orf12 locus were identical for a very small region, closest to the mutation, suggesting an old founder effect, or, two independent founders. The clinical phenotype was characterized by adult onset in most cases (mean 24.5 years, range 10-36), and broad spectrum, including prominent parkinsonism, pyramidal signs, psychiatric disturbances, cognitive decline, and motor neuropathy. On T2- or susceptibility weighted-MRI images, all patients displayed bilateral hypointensities in globus pallidus and substantia nigra, without an eye-of-the-tiger sign; however, hyperintense streaking of the medial medullary lamina between the external and internal parts of globus pallidus was observed frequently.

Conclusions: The C19orf12 p.Thr11Met mutation is frequent among adult Turkish patients with MPAN. These findings contribute to the characterization of this important NBIA form, and have direct implications for genetic testing of patients of Turkish origin.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/c19orf12-p-thr11met-mutation-is-frequent-among-adult-turkish-patients-with-mpan/