c. 601–603 deletion, p. Arg201del (Ghezzi et al.,,2010Ghezzi D, Sevrioukova I, Invernizzi F, Lamperti C, Mora M, D’Adamo P, Novara F, Zuffardi O, Uziel G and Zeviani M (2010) Severe X-linked mitochondrial encephalomyopathy associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 86:639-649.) |
Mitochondrial encephalomyopathy (FAD domain) |
Y |
Seizures |
Swallowing difficulties; dysarthria; progressive muscle weakness; decreased limb reflexes; psychomotor regression |
Reduction of respiratory chain (RC) cIII and cIV |
Increased apoptotic rates |
c.727G>T, p. Val243Leu (Kettwig et al.,2015Kettwig M, Schubach M, Zimmermann FA, Klinge L, Mayr JA, Biskup S, Sperl W, Gartner J and Huppke P (2015) From ventriculomegaly to severe muscular atrophy: expansion of the clinical spectrum related to mutations in AIFM1. Mitochondrion 21:12-18.) |
Ventriculomegaly + peripheral neuropathy? (FAD domain) |
Y |
Seizures |
Swallowing difficulties; dysarthria; progressive muscle weakness; decreased limb reflexes; ataxia; psychomotor regression |
NA |
NA |
c.923G>A, p.Gly308Glu (Berger et al.2011Berger I, Ben-Neriah Z, Dor-Wolman T, Shaag A, Saada A, Zenvirt S, Raas-Rothschild A, Nadjari M, Kaestner KH and Elpeleg O (2011) Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing. Mol Genet Metab 104:517-520.) |
Prenatal ventriculomegaly (NADH domain) |
NA |
Seizures |
Swallowing difficulties; progressive muscle weakness; psychomotor regression; cardiac involvement |
NA |
NA |
c.1030C>T, p.Leu344Phe (Zong et al.,2015Zong L, Guan J, Ealy M, Zhang Q, Wang D, Wang H, Zhao Y, Shen Z, Campbell CA, Wang F et al. (2015) Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder. J Med Genet 52:523-531.) |
Auditory neuropathy+ peripheral neuropathy (NADH domain) |
Y |
N |
Unsteadiness; Numbness of extremities |
NA |
NA |
c.1463C>T p.Pro488Leu (this study) |
Hearing loss + peripheral neuropathy (C-terminal domain) |
Y |
N |
Progressive muscle weakness; decreased limb reflexes; ataxia; psychomotor regression |
NA |
Mildly increased apoptotic rates |
c.1478A>T, p.Glu493Val (Rinaldi et al.,,2012Rinaldi C, Grunseich C, Sevrioukova IF, Schindler A, Horkayne-Szakaly I, Lamperti C, Landoure G, Kennerson ML, Burnett BG, Bonnemann C et al. (2012) Cowchock syndrome is associated with a mutation in apoptosis-inducing factor. Am J Hum Genet 91:1095-1102.) |
Hearing loss + peripheral neuropathy (C-terminal domain) |
Y |
N |
Progressive muscle weakness; decreased limb reflexes; ataxia; psychomotor regression |
Slight structural changes, abnormal propensity to NADH reduction and O2 oxidation; faster oxidation |
Higher affinity for binding to DNA and increased apoptotic rates |
c.1288C>T, p.Arg430Cys (Zong et al.,2015Zong L, Guan J, Ealy M, Zhang Q, Wang D, Wang H, Zhao Y, Shen Z, Campbell CA, Wang F et al. (2015) Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder. J Med Genet 52:523-531.) |
Auditory neuropathy (FAD domain) |
Y |
N |
N |
NA |
NA |