American journal of human genetics, 02 November 2017, Vol.101(5), pp.833-843
Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650GA (p.Arg217His) and c.649CT (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands’ cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2). The same effect was observed after overexpression of the mutant...
Gorlin-Chaudhry-Moss Syndrome ; Oxidative Stress ; Mitochondrial Swelling ; Craniosynostosis ; Hypertrichosis ; Slc25a24 ; Premature Aging ; Cutis Laxa ; Lipoatrophy ; Gorlin-Chaudhry-Moss Syndrome ; Oxidative Stress ; Mitochondrial Swelling ; Craniosynostosis ; Hypertrichosis ; Slc25a24 ; Premature Aging ; Cutis Laxa ; Lipoatrophy ; Biology
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