Vella 2018 MiPschool Tromso C4

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Joanna Vella
Exome analysis sheds light on mitochondrial disorders.

Link: MitoEAGLE

Vella J, Laurie S, Matalonga L, Borg J, Soler D, Vella N, Aquilina J, Said E, Borg I, Felice A (2018)

Event: MiPschool Tromso-Bergen 2018


The Malta BioBank ( [1], participated in the collaborative BBMRI-Large Prospective Cohort (BBMRI-LPC) whole exome sequencing (WES) call, jointly organised by BBMRI-LPC, EuroBioBank, RD-Connect and Centro Nacional de AnΓ‘lisis GenΓ³mico (CNAG-CRG). The main objective was to identify the molecular pathology of 50 genetically undiagnosed patients with mitochondrial disorders by WES (MITOMUTWES).

50 patient samples were identified from the RD-Connect sample catalogue [2]. These were located in the Malta BioBank and Hacettepe University, Turkey, both of which form part of the EuroBioBank rare disease network. The Maltese cohort included 13 probands (7 children and 6 adults) and 2 unaffected relatives. WES was carried out at CNAG-CRG. Phenotypic information of each patient was recorded on the RD-Connect PhenoTips instance [3]. Bio-informatics analysis was undertaken using the RD-Connect Genome-Phenome Analysis Platform [4].

A critical analysis of rare nuclear and mitochondrial (MT) gene mutations was performed. 10 patients were carriers for more than one rare variant with no clear candidates. 3 cases were found to have: i) a mis-sense mutation c.308C>T (rs749249430) in NDUFAF3 that caused Mitochondrial Complex 1 deficiency (MC1d); ii) a splice donor and two mis-sense variants: c.207+2T>G (rs782792601), c.206A>G (rs781909386) and c.205A>G (rs782503581) in NDUFB11 that affected the exon-splice site and is also thought to cause MC1d; iii) the MT variant m.3243A>G mutation (rs199474657) that caused Mitochondrial myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS), and another variant m.4336T>C (rs41456348) that caused the splice site and sensinueronal deafness and migraine.

Whole exome sequencing served to establish a genetic diagnosis in 3 of the 13 Maltese rare disease patients. A combined genomic and transcriptomic approach will be used to identify candidate modifier genes that may play a crucial role in the development and / or modification of the clinical phenotype. This integrative analysis will characterise the effect of these gene mutations on mitochondrial function.

β€’ Bioblast editor: Plangger M


Vella J(1,2), Laurie S(3), Matalonga L(3), Borg J(1,4), Soler D(5), Vella N(6), Aquilina J(5), Said E(5), Borg I(2,5), Felice A(1,2,5)

  1. The Malta BioBank
  2. Dept Physiology Biochemstry, Pathology, Fac Medicine Surgery; Univ Malta, Msida, Malta
  3. Centro Nacional AnΓ‘lisis GenΓ³mico, Center Genomic Regulation, Barcelona Inst Science Technology, Univ Pompeu Fabra, Barcelona, Spain
  4. Dept Applied Biomedical Science, Fac Health Sciences, Univ Malta
  5. Dept Paediatrics, Neuroscience Pathology, Mater Dei Hospital; Msida, Malta. - [email protected]



Labels: MiParea: mtDNA;mt-genetics, nDNA;cell genetics 

Stress:Mitochondrial disease  Organism: Human 

Event: C4, Oral 

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