A rare male patient with Fontaine progeroid syndrome caused by p.R217H de novo mutation in <i>SLC25A24</i>

Rodríguez‐García, María Elena; Cotrina‐Vinagre, Francisco Javier; Cruz-Rojo, Jaime; Garzón-Lorenzo, Lucía; Carnicero-Rodríguez, Patricia; Pozo, Jaime Sánchez-Del; Martı́nez-Azorı́n, Francisco

doi:10.1002/ajmg.a.40496

Cited by 15 publications

(25 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Segmental progeroid syndromes, defined as syndromes with signs of premature aging affecting more than one tissue or organ (Martin 1978), are highly heterogenous genetic disorders. Studies utilizing next-generation sequencing (NGS) approaches have revealed several novel progeroid genes in recent years (Ehmke et al 2017;Jay et al 2016;Lessel et al 2014bLessel et al , 2017bLessel et al , 2018Marbach et al 2019;Paolacci et al 2018;Puente et al 2011;Schrauwen et al 2015;Wambach et al 2018), and broadened the spectrum of phenotypes of many known progeroid conditions and the number of associated genetic causes (Lessel et al 2014a(Lessel et al , 2015Rodriguez-Garcia et al 2018;Soria-Valles et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

et al. 2020

View full text Add to dashboard Cite

Biallelic variants in TOR1AIP1, encoding the integral nuclear membrane protein LAP1 (lamina-associated polypeptide 1) with two functional isoforms LAP1B and LAP1C, have initially been linked to muscular dystrophies with variable cardiac and neurological impairment. Furthermore, a recurrent homozygous nonsense alteration, resulting in loss of both LAP1 isoforms, was identified in seven likely related individuals affected by multisystem anomalies with progeroid-like appearance and lethality within the 1st decade of life. Here, we have identified compound heterozygosity in TOR1AIP1 affecting both LAP1 isoforms in two unrelated individuals affected by congenital bilateral hearing loss, ventricular septal defect, bilateral cataracts, mild to moderate developmental delay, microcephaly, mandibular hypoplasia, short stature, progressive muscular atrophy, joint contractures and severe chronic heart failure, with much longer survival. Cellular characterization of primary fibroblasts of one affected individual revealed absence of both LAP1B and LAP1C, constitutively low lamin A/C levels, aberrant nuclear morphology including nuclear cytoplasmic channels, and premature senescence, comparable to findings in other progeroid forms of nuclear envelopathies. We additionally observed an abnormal activation of the extracellular signal-regulated kinase 1/2 (ERK 1/2). Ectopic expression of wild-type TOR1AIP1 mitigated these cellular phenotypes, providing further evidence for the causal role of identified genetic variants. Altogether, we thus further expand the TOR1AIP1associated phenotype by identifying individuals with biallelic loss-of-function variants who survived beyond the 1st decade of life and reveal novel molecular consequences underlying the TOR1AIP1-associated disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

et al. 2020

View full text Add to dashboard Cite

show abstract

“…For example, SLC25A24 encodes a carrier protein that mediates electroneutral exchange of Mg-ATP or Mg-ADP against phosphate ions, is responsible for low fat mass in humans and mice (Urano et al, 2015), and is also related with bovine embryonic mortality (Killeen et al, 2016). Mutations in SLC25A24 have been found to be associated with fontaine progeroid syndrome in humans (Rodríguez-García et al, 2018). Furthermore, STXBP3 (also known as Munc18c), involved in insulin-regulated GLUT4 trafficking, has been found to be positively associated with body weight in Large White and Tongcheng pigs (Li et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study and Fine Mapping Reveals Candidate Genes for Birth Weight of Yorkshire and Landrace Pigs

Yang

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Birth weight of pigs is an important economic factor in the livestock industry. The identification of the genes and variants that underlie birth weight is of great importance. In this study, we integrated two genotyping methods, single nucleotide polymorphism (SNP) chip analysis and restriction site associated DNA sequencing (RAD-seq) to genotype genome-wide SNPs. In total, 45,175 and 139,634 SNPs were detected with the SNP chip and RAD-seq, respectively. The genome-wide association study (GWAS) of the combined SNP panels identified two significant loci located at chr1: 97,745,041 and chr4: 112,031,589, that explained 6.36% and 4.25% of the phenotypic variance respectively. To reduce interval containing causal variants, we imputed sequencelevel SNPs in the GWAS identified regions and fine-mapped the causative variants into two narrower genomic intervals: a ∼100 kb interval containing 71 SNPs and a broader ∼870 kb interval with 432 SNPs. This fine-mapping highlighted four promising candidate genes, SKOR2, SMAD2, VAV3, and NTNG1. Additionally, the functional genes, SLC25A24, PRMT6 and STXBP3, are also located near the fine-mapping region. These results suggest that these candidate genes may have contribute substantially to the birth weight of pigs.

show abstract

“…The exchange is essential for normal energy production, the metabolism of various molecules, and protein production within cells. SLC25A24 is involved in carcinogenesis (18) and the Fontaine progeroid syndrome (19).…”

Section: Discussionmentioning

confidence: 99%

Three Poliovirus Sequences in the Human Genome Associated With Colorectal Cancer

Lehrer

Rheinstein²

2018

Cancer Genomics Proteomics

View full text Add to dashboard Cite

Background/Aim: In a previous study we analyzed poliomyelitis incidence in US states, before the introduction of the polio vaccine. We noted an inverse correlation between polio incidence in US states, between 1937 and 1951, and colorectal cancer incidence (2005-2009). To further elucidate the role that poliovirus could play in colorectal cancer, the full human genome for poliovirus sequences was analyzed using the UCSC Genome Browser. Materials and Methods: BLAT, the Blast-Like Alignment Tool of the UCSC Genome Browser, was used to compare the poliovirus genome to the human genome. Results: BLAT revealed three poliovirus sequences in three chromosomes: Chromosome 20p12.1 (MACROD2 gene), chromosome 1p13.3 (SLC25A24 gene), and chromosome 2p25.1. Conclusion: Poliovirus sequences in the human genome may contribute to programmed cell death and lysis of colorectal cancer cells. A recombinant poliovirus, incapable of reverting to neurovirulence, might be given orally at intervals as a colorectal cancer vaccine to prevent colorectal cancer.

show abstract

A rare male patient with Fontaine progeroid syndrome caused by p.R217H de novo mutation in SLC25A24

Cited by 15 publications

References 15 publications

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

Two novel cases further expand the phenotype of TOR1AIP1-associated nuclear envelopathies

Genome-Wide Association Study and Fine Mapping Reveals Candidate Genes for Birth Weight of Yorkshire and Landrace Pigs

Three Poliovirus Sequences in the Human Genome Associated With Colorectal Cancer

Contact Info

Product

Resources

About