Background: In 2009, we identified TACO1 as a novel mitochondrial disease gene in a single family, however no second family has been described to confirm the role of TACO1 in mitochondrial disease.
Objective: In this report, we describe two independent consanguineous families carrying pathogenic variants in TACO1, confirming the phenotype.
Methods: Detailed clinical investigations and whole exome sequencing with haplotype analysis have been performed in several members of the two reported families.
Results: Clinical phenotype of the patients confirms the originally reported phenotype of a childhood-onset progressive cerebellar and pyramidal syndrome with optic atrophy and learning difficulties. Brain MRI showed periventricular white matter lesions with multiple cystic defects, suggesting leukoencephalopathy in both patients. One patient carried the previously described homozygous TACO1 variant (p.His158ProfsTer8) and haplotype analysis suggested that this variant is a rare founder mutation. The second patient from another family carried a homozygous novel frame shift variant (p.Cys85PhefsTer15).
Conclusions: The identification of two Turkish families with similar characteristic clinical presentation and an additional homozygous nonsense mutation confirms that TACO1 is a human mitochondrial disease gene. Although most patients with this clinical presentation undergo next generation sequencing analysis, screening for selected founder mutations in the Turkish population based on the precise clinical presentation may reduce time and cost of finding the genetic diagnosis even in the era of massively parallel sequencing.
C1 [Oktay, Yavuz; Sonmezler, Ece; Yilmaz, Elmasnur; Hiz, Semra] Dokuz Eylul Univ, Izmir Biomed & Genome Ctr, Hlth Campus, Izmir, Turkey.
[Oktay, Yavuz; Sonmezler, Ece; Yilmaz, Elmasnur] Dokuz Eylul Univ, Izmir Int Biomed & Genome Inst, Izmir, Turkey.
[Gungor, Serdal] Inonu Univ, Fac Med, Turgut Ozal Res Ctr, Dept Paediat Neurol, Malatya, Turkey.
[Zeltner, Lena; Wiethoff, Sarah; Schoels, Ludger; Kaemereit, Sofie; Liepelt, Inga; Schuele, Rebecca] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Zeltner, Lena; Wiethoff, Sarah; Schoels, Ludger; Kaemereit, Sofie; Liepelt, Inga; Schuele, Rebecca] Univ Tubingen, Ctr Neurol, Tubingen, Germany.
[Schoels, Ludger; Liepelt, Inga; Schuele, Rebecca] Univ Tubingen, German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany.
[Munro, Benjamin; Horvath, Rita] Univ Cambridge, Sch Clin Med, Dept Clin Neurosci, Level 3 A Block,Box 165,Cambridge Biomed Campus, Cambridge CB2 0QQ, England.
[Bender, Benjamin] Univ Tubingen, Diagnost & Intervent Neuroradiol Radiol Clin, Tubingen, Germany.
[Kernstock, Christoph] Univ Tubingen, Univ Eye Hosp Tubingen, Ctr Ophthalmol, Tubingen, Germany.
[Topf, Ana] Newcastle Univ, John Waltom Muscular Dystrophy Res Ctr, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England.
[Yis, Uluc; Hiz, Semra] Dokuz Eylul Univ, Sch Med, Dept Paediat Neurol, Izmir, Turkey.
[Laurie, Steven; Lochmueller, Hanns] Barcelona Inst Sci & Technol, Ctr Genom Regulat, CNAG CRG, Barcelona, Spain.
[Yaramis, Ahmet] Private Off, Pediat Neurol Clin, Diyarbakir, Turkey.
[Zuchner, Stephan] Univ Miami, Miller Sch Med, Dept Human Genet, Miami, FL 33136 USA.
[Zuchner, Stephan] Univ Miami, Miller Sch Med, Hussman Inst Human Genom, Miami, FL 33136 USA.
[Lochmueller, Hanns] Univ Freiburg, Fac Med, Med Ctr, Dept Neuropediat & Muscle Disorders, Freiburg, Germany.
[Lochmueller, Hanns] Childrens Hosp Eastern Ontario, Res Inst, Ottawa, ON, Canada.
[Lochmueller, Hanns] Ottawa Hosp, Dept Med, Div Neurol, Ottawa, ON, Canada.
[Lochmueller, Hanns] Univ Ottawa, Brain & Mind Res Inst, Ottawa, ON, Canada.