Sequence variation in PPP1R13L results in a novel form of cardio‐cutaneous syndrome

Abstract

The accession numbers for the reported data were inadvertently omitted. The authors apologize for this oversight and any inconvenience caused, and hereby provide the missing information:The raw and processed data are all available at ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) under the accession numbers: E-MTAB-5812 (for the results from the 7-and 12-week-old mice and for the in vivo treatment with LPS), and E-MTAB-5826 (for the results from the knocked down cardiomyocytes). The accession number for the causative sequence variation is available at ClinVar (https://www. ncbi.nlm.nih.gov/clinvar/) under accession number SCV000579451.

Cell autonomous role of iASPP deficiency in causing cardiocutaneous disorders

“…An interesting finding was that the eye phenotypes in both germline and K14-Cre iASPP-deficient mice are similar to those observed in patients and in fetuses aborted between 21 and 31 weeks of gestation with iASPP mutations [11]. The morphogenetic process of eyelid closure in humans parallels that in mice, though in humans this process occurs in utero between weeks 7-25 weeks of gestation.…”

“…Eyelid closure defects at birth and corneal opacity in adult mice are two of the main features of germline iASPP deficiency that occur with full penetrance [12,33]. Importantly, cloudy cornea has also been reported in 1 of 3 examined patients with an iASPP-null mutation, and eye abnormalities have been found in all 4 examined aborted fetuses with iASPP mutations [11].…”

“…A recently identified single gene mutation that causes cardiocutaneous syndrome (and cardiocutaneous disorder in cattle and mice) is PPP1R13L [11][12][13][14][15], which encodes inhibitor of apoptosis stimulating p53 protein (iASPP), an evolutionarily conserved inhibitor of p53 and p63 [16,17]. iASPP is a regulator of desmosomes [13], but is also implicated in inflammatory pathways [11,18]. For example, iASPP was originally identified as a binding partner for NF-κB in a yeast two-hybrid assay [18] and, consistent with this, iASPP-deficiency in patients and mice results in elevated expression of inflammation-related genes, some of which are NF-κB targets [11,12].…”

“…iASPP is a regulator of desmosomes [13], but is also implicated in inflammatory pathways [11,18]. For example, iASPP was originally identified as a binding partner for NF-κB in a yeast two-hybrid assay [18] and, consistent with this, iASPP-deficiency in patients and mice results in elevated expression of inflammation-related genes, some of which are NF-κB targets [11,12]. Given that iASPP is ubiquitously expressed and germline mutations in the iASPP gene could affect the function of all iASPP-expressing cells as well as the multiple pathways it regulates, a key challenge is to identify the molecular mechanisms by which the faulty gene causes the observed phenotype.…”

“…Therefore, shuttling of iASPP between cell-cell junctions and the nucleus could have profound effects on desmosome stability and nuclear gene expression [20], and loss of both junctional and nuclear iASPP could be important in cardiocutaneous syndrome. For example, loss of nuclear iASPP could result in activation of NF-κB in certain cell types leading to enhanced secretion and activity of inflammatory mediators [11], whereas loss of cell-junctional iASPP could result in desmosome instability [13].…”