De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise

Writzl, Karin; Maver, Aleš; Kovačič, Lidija; Martínez-Valero, Paula; Contreras, Laura; Satrústegui, Jorgina; Castori, Marco; Faivre, Laurence; Lapunzina, Pablo; Kuilenburg, André B. P.; Radović, Slobodanka; Thauvin‐Robinet, Christel; Peterlin, Borut; Arco, Araceli del; Hennekam, Raoul C. M.

doi:10.1016/j.ajhg.2017.09.017

Cited by 55 publications

(83 citation statements)

References 56 publications

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“…49,[52][53][54] In the accompanying article in this issue of The American Journal of Human Genetics, Writzl et al report the same c.650G>A and c.649C>T mutations in SLC25A24 but in association with Petty-type congenital progeroid syndrome, referred to as Fontaine syndrome. 55 Both phenotypes show overlapping clinical features (such as growth retardation, craniosynostosis, reduced subcutaneous fat, and small distal phalanges) but differ in some facial characteristics. The most striking difference is the early demise in Fontaine syndrome and a mostly normal lifespan in GCMS.…”

mentioning

confidence: 99%

De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction

Ehmke

Graul‐Neumann

Smorag

et al. 2017

The American Journal of Human Genetics

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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.650G>A (p.Arg217His) and c.649C>T (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/P 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 (HO). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands' fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon HO exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/P transport to the development of skeletal and connective tissue.

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confidence: 99%

De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction

Ehmke

Graul‐Neumann

Smorag

et al. 2017

The American Journal of Human Genetics

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“…Other features observed were severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, short distal phalanges, lipoatrophy, and cutis laxa [Ehmke et al, 2017]. The same mutations were also identified in 4 cases with Fontaine syndrome (OMIM 612289), 2 of them had craniosynostosis [Writzl et al, 2017]. Ehmke et al [2017] assume that the mutations influence the formation or opening of the mitochondrial permeability transition pore leading to an increased sensitivity of the mitochondria to oxidative stress.…”

Section: Slc25a24mentioning

confidence: 82%

Genetic Causes of Craniosynostosis: An Update

Goos

Mathijssen²

2018

Mol Syndromol

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In 1993, Jabs et al. were the first to describe a genetic origin of craniosynostosis. Since this discovery, the genetic causes of the most common syndromes have been described. In 2015, a total of 57 human genes were reported for which there had been evidence that mutations were causally related to craniosynostosis. Facilitated by rapid technological developments, many others have been identified since then. Reviewing the literature, we characterize the most common craniosynostosis syndromes followed by a description of the novel causes that were identified between January 2015 and December 2017.

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“…A 3'UTR SNP was identified in a gene coding for SLC25A24. Mice fed a high-fat diet exhibited increased expression level of SLC25A24; whereas, adipocyte differentiation was suppressed in Slc25a24-knockout [85].…”

Section: Unique Genes Affecting the Additive Genetic Variance For Moimentioning

confidence: 97%

Genome-Wide Scan For Common Variants Associated With Intramuscular Fat And Moisture Content In Rainbow Trout

Ali

Al-Tobasei

Lourenço³

et al. 2020

Preprint

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Genetic improvement of fillet quality attributes is a priority of the aquaculture industry. Muscle composition impacts quality attributes such as flavor, appearance, texture, and juiciness. Fat and moisture make up about 80% of the tissue weight. The genetic architecture underlying the fat and moisture content of the muscle are still to be fully explored in fish. A 50K gene transcribed SNP chip was used for genotyping 789 fish with available phenotypic data for fat and moisture content. Genotyped fish were obtained from two consecutive generations produced in the NCCCWA growth-selective breeding program. Estimates of SNP effects from weighted single-step GBLUP (WssGBLUP) were used to perform genome-wide association (GWA) analysis to identify quantitative trait loci (QTL) associated with the studied traits. Using genomic sliding windows of 50 adjacent SNPs, 137 and 178 SNPs were identified as associated with fat and moisture content, respectively. Chromosomes 19 and 29 harbored the highest number of SNPs explaining at least 2% of the genetic variation in fat and moisture content. A total of 61 common SNPs on chromosomes 19 and 29 affected the aforementioned traits; this association suggests common mechanisms underlying intramuscular fat and moisture content. Additionally, based on single-marker GWA analyses, 8 and 24 SNPs were identified in association with fat and moisture content, respectively. SNP-harboring genes were primarily involved in lipid metabolism, cytoskeleton remodeling, and protein turnover. This work provides putative SNP markers that could be prioritized and used for genomic selection in breeding programs.

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De Novo Mutations in SLC25A24 Cause a Disorder Characterized by Early Aging, Bone Dysplasia, Characteristic Face, and Early Demise

Cited by 55 publications

References 56 publications

De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction

De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction

Genetic Causes of Craniosynostosis: An Update

Genome-Wide Scan For Common Variants Associated With Intramuscular Fat And Moisture Content In Rainbow Trout

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