, Volume 18, Issue 4, pp 245–250 | Cite as

A newly distal hereditary motor neuropathy caused by a rare AIFM1 mutation

  • Paula Sancho
  • Ana Sánchez-Monteagudo
  • Antonio Collado
  • Clara Marco-Marín
  • Cristina Domínguez-González
  • Ana Camacho
  • Erwin Knecht
  • Carmen EspinósEmail author
  • Vincenzo Lupo
Short Communication


In two siblings, who suffer from an early childhood-onset axonal polyneuropathy with exclusive involvement of motor fibers, the c.629T>C (p.F210S) mutation was identified in the X-linked AIFM1 gene, which encodes for the apoptosis-inducing factor (AIF). The mutation was predicted as deleterious, according to in silico analysis. A decreased expression of the AIF protein, altered cellular morphology, and a fragmented mitochondrial network were observed in the proband’s fibroblasts. This new form of motor neuropathy expands the phenotypic spectrum of AIFM1 mutations and therefore, the AIFM1 gene should be considered in the diagnosis of hereditary motor neuropathies.


Inherited peripheral neuropathies AIFM1 Apoptosis inducing factor Gene panel Mitochondrial disorder 



We are grateful to the patients and their parents who participated in this study. This project was funded by the Instituto de Salud Carlos III (ISCIII)–FEDER (grant nos. PI12/00453 and PI15/00187). P.S. has a FPU grant funded by the Ministerio de Educación, Cultura y Deporte (grant no. FPU15/00964). A.S.M. has a grant funded by the Fundació per amor a l’art (FPAA). C.E. has a “Miguel Servet” contract funded by the ISCIII and Centro de Investigación Príncipe Felipe (CIPF) (grant no. CPII14/00002). The Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) is an initiative from the ISCIII.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10048_2017_524_Fig2_ESM.gif (5 kb)
Supplementary Figure S1

Pedigree structure of the studied family. The arrow indicates the proband (Patient 1). (GIF 5 kb)

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High resolution image (TIFF 3561 kb).
10048_2017_524_Fig3_ESM.gif (27 kb)
Supplementary Figure S2

Bright-field microscopy visualization, showing normal healthy control (Ct) and abnormal patient’s fibroblasts (Pt) morphology. (GIF 26 kb)

10048_2017_524_MOESM2_ESM.tif (3.5 mb)
High-resolution image (TIFF 3559 kb).
10048_2017_524_Fig4_ESM.gif (38 kb)
Supplementary Figure S3

a Multiple alignments of orthologous sequences across seven organisms. b Bioinformatics results for the characterized AIFM1 amino acid substitution using several predictors for pathogenicity. (GIF 38 kb)

10048_2017_524_MOESM3_ESM.tif (2.4 mb)
High-resolution image (TIFF 2409 kb).
10048_2017_524_Fig5_ESM.gif (7 kb)
Supplementary Figure S4

qPCR relative quantification of AIFM1 in patient (Pt) and two controls (Ct1: female; Ct2: male) fibroblasts’. Error bars represent SEM. (GIF 7 kb)

10048_2017_524_MOESM4_ESM.tif (971 kb)
High-resolution image (TIFF 971 kb).
10048_2017_524_MOESM5_ESM.docx (15 kb)
Supplementary Table 1 (DOCX 14 kb)
10048_2017_524_MOESM6_ESM.docx (13 kb)
ESM 1 (DOCX 13 kb)


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Paula Sancho
    • 1
    • 2
  • Ana Sánchez-Monteagudo
    • 1
    • 2
  • Antonio Collado
    • 1
    • 2
  • Clara Marco-Marín
    • 3
    • 4
  • Cristina Domínguez-González
    • 5
  • Ana Camacho
    • 6
    • 7
  • Erwin Knecht
    • 2
    • 4
    • 8
  • Carmen Espinós
    • 1
    • 2
    • 9
    Email author return OK on get
  • Vincenzo Lupo
    • 1
    • 2
    • 9
  1. 1.Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF)ValenciaSpain
  2. 2.INCLIVA & IIS La Fe Rare Diseases Joint UnitsValenciaSpain
  3. 3.Instituto de Biomedicina de Valencia (IBV)–CSICValenciaSpain
  4. 4.Centro de Investigación Biomédica en Red sobre Enfermedades Raras (CIBERER)–ISCIIIValenciaSpain
  5. 5.Unit of NeuromuscularInstituto de Investigación i+12MadridSpain
  6. 6.Department of NeuropediatricsHospital Universitario 12 de OctubreMadridSpain
  7. 7.Faculty of MedicineUniversidad Complutense de Madrid (UCM)MadridSpain
  8. 8.Unit of Intracellular Protein DegradationCentro de Investigación Príncipe Felipe (CIPF)ValenciaSpain
  9. 9.Department of Genomics and Translational GeneticsCentro de Investigación Príncipe Felipe (CIPF)ValenciaSpain

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