3697G>A in MT-ND1 is a causative mutation in mitochondrial disease

Lucía Spangenberg; Martin Graña; Gonzalo Greif; Juan Suarez-Rivero; Karina Krysztal; Alejandra Tapié; María Boidi; Valeria Fraga; Aída Lemes; Rosario Gueçaimburú; Alfredo Cerisola; José Sánchez-Alcázar; Carlos Robello; Víctor Raggio; Hugo Naya

doi:10.1016/j.mito.2016.03.006

Journal articles

3697G>A in MT-ND1 is a causative mutation in mitochondrial disease

Lucía Spangenberg ¹ Martin Graña ¹ Gonzalo Greif ¹ Juan Suarez-Rivero ^{2, 3} Karina Krysztal ⁴ Alejandra Tapié ⁵ María Boidi ⁵ Valeria Fraga ⁶ Aída Lemes ⁷ Rosario Gueçaimburú ⁵ Alfredo Cerisola ⁸ José Sánchez-Alcázar ^{2, 3} Carlos Robello ¹ Víctor Raggio ⁵ Hugo Naya ^{1, *}

* Corresponding author

1 Institut Pasteur de Montevideo

2 UPO - Universidad Pablo de Olavide [Sevilla]

3 CIBER de Enfermedades Raras (CIBERER)

4 UDELAR - UDELAR, Facultad de Ingenieria [Montevideo]

5 UCUR - Universidad de la República [Montevideo]

6 SMI - Servicio Medico Integral [Montevideo]

7 Hospital Italiano de Montevideo

8 Centro de Rehabilitación Infantil Teletón [Montevideo]

Abstract : Mitochondrial diseases are a group of clinically heterogeneous disorders that can be difficult to diagnose. We report a two and a half year old girl with clinical symptoms compatible with Leigh disease but with no definitive diagnosis. Using next generation sequencing we found that mutation 3697G>A was responsible for the patient's clinical symptoms. Corroboration was performed via segregation analysis in mother and sister and by evolutionary analysis that showed that the mutation is located in a highly conserved region across a wide range of species. Functional analyses corroborated the mutation effect and indicated that the pathophysiological alterations were partially restored by Coenzyme Q10. In addition, we proposed that the presence of the mutation at high frequencies causes the phenotype in the patient, while other family members with intermediate levels of heteroplasmy are symptoms-free.

Keywords : Heteroplasmy Clinical genomics Leigh disease Mitochondrial disease Next Generation Sequencing

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

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https://hal-riip.archives-ouvertes.fr/pasteur-01880466
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Submitted on : Monday, September 24, 2018 - 9:04:00 PM
Last modification on : Monday, October 8, 2018 - 5:44:06 PM

3697G>A in MT-ND1 is a causative mutation in mitochondrial disease

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3697G>A in MT-ND1 is a causative mutation in mitochondrial disease

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