Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing

Berger, Itai; Ben‐Neriah, Ziva; Dor-Wolman, Talia; Shaag, Avraham; Saada, Ann; Zenvirt, Shamir; Raas‐Rothschild, Annick; Nadjari, M.; Kaestner, Klaus H.; Elpeleg, Orly

doi:10.1016/j.ymgme.2011.09.020

Cited by 81 publications

(77 citation statements)

References 12 publications

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“…Thus far it is not known 116 whether the redox activity of AIF (which is an NADH oxidase) directly affects CHCHD4 as 117 an electron acceptor. 118 …”

Section: Elusive 92 93mentioning

confidence: 99%

“…While full knockout of AIF or 312 CHCHD4 are embryonic lethal [40,115], distinct AIF point mutations induce an array of 313 human diseases ranging from severe X-linked mitochondrial encephalomyopathy, Cowchock 314 syndrome (X-linked Charcot-Marie-Tooth disease with axonal sensorimotor neuropathy, 315 deafness and cognitive impairment) to infantile motor neuron disease or auditory neuropathy 316 spectrum disorder [116][117][118][119]. The fact that at least one of these pathogenic AIF mutations 317 (G308E, which gives rise to a severe phenotype) reduces AIF binding to CHCHD4 [40], 318 underscores the physiological importance of the AIF-CHCHD4 interaction.…”

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confidence: 99%

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Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease

Modjtahedi

Tokatlidis

Dessen

et al. 2016

Trends in Biochemical Sciences

108

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Members of the coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing protein family that carry (CX 9 C) type motifs are imported into the mitochondrion with the help of the disulfide relay-dependent MIA import pathway. These evolutionary-conserved proteins are emerging as new cellular factors that control mitochondrial respiration, redox regulation, lipid homeostasis or membrane ultrastructure and dynamics. Here, we discuss recent insights on the activity of known (CX 9 C) motif-carrying proteins in mammals and review current data implicating the MIA40/CHCHD4 import machinery in the regulation of their mitochondrial import. Recent findings and the identification of disease-associated mutations in specific (CX 9 C) motif-carrying proteins have highlighted members of this family of proteins as potential therapeutic targets in a variety of human disorders.

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“…Thus far it is not known 116 whether the redox activity of AIF (which is an NADH oxidase) directly affects CHCHD4 as 117 an electron acceptor. 118 …”

Section: Elusive 92 93mentioning

confidence: 99%

mentioning

confidence: 99%

Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease

Modjtahedi

Tokatlidis

Dessen

et al. 2016

Trends in Biochemical Sciences

108

View full text Add to dashboard Cite

show abstract

“…Such mutants cause X-linked pathologies that resemble mitochondriopathies with regard to their clinical manifestations ranging from deafness and cognitive impairment to severe encephalomyopathy and cardiomyopathy. [19][20][21][22][23] The mechanisms accounting for mitochondrial defect induced by deficient AIF expression have recently been elucidated. 24 Thus, AIF is required for the translational import of a mitochondrial intermembrane protein called coiled-coil-helix-coiled-coilhelix domain containing 4 (CHCHD4).…”

Section: Introductionmentioning

confidence: 99%

Metabolic epistasis among apoptosis-inducing factor and the mitochondrial import factor CHCHD4

et al. 2015

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“…Subsequently, four fetuses were included in a cohort of 250 patients with Mendelian disorders who were exome sequenced, of which one was successfully diagnosed (5). There are other cases in which postnatal exome sequencing of cohorts with specific diseases first manifesting in the prenatal period have yielded diagnoses (36,37). Our study of a cohort of 30 fetuses with diverse abnormalities has allowed us to estimate the current diagnostic yield of exome sequencing for fetal abnormalities as being broadly equivalent to aCGH, which is 10% (2 -4).…”

Section: Discussionmentioning

confidence: 99%

2.3 Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound

Hillman

Carss

McMullan³

et al. 2014

Arch Dis Child Fetal Neonatal Ed

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The genetic etiology of non-aneuploid fetal structural abnormalities is typically investigated by karyotyping and array-based detection of microscopically detectable rearrangements, and submicroscopic copy-number variants (CNVs), which collectively yield a pathogenic finding in up to 10% of cases. We propose that exome sequencing may substantially increase the identification of underlying etiologies. We performed exome sequencing on a cohort of 30 non-aneuploid fetuses and neonates (along with their parents) with diverse structural abnormalities first identified by prenatal ultrasound. We identified candidate pathogenic variants with a range of inheritance models, and evaluated these in the context of detailed phenotypic information. We identified 35 de novo single-nucleotide variants (SNVs), small indels, deletions or duplications, of which three (accounting for 10% of the cohort) are highly likely to be causative. These are de novo missense variants in FGFR3 and COL2A1, and a de novo 16.8 kb deletion that includes most of OFD1. In five further cases (17%) we identified de novo or inherited recessive or X-linked variants in plausible candidate genes, which require additional validation to determine pathogenicity. Our diagnostic yield of 10% is comparable to, and supplementary to, the diagnostic yield of existing microarray testing for large chromosomal rearrangements and targeted CNV detection. The de novo nature of these events could enable couples to be counseled as to their low recurrence risk. This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic abnormalities through the application of next-generation sequencing.

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Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing

Cited by 81 publications

References 12 publications

Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease

Mitochondrial Proteins Containing Coiled-Coil-Helix-Coiled-Coil-Helix (CHCH) Domains in Health and Disease

Metabolic epistasis among apoptosis-inducing factor and the mitochondrial import factor CHCHD4

2.3 Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound

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