Immunome Research
Open Access

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

8^th Molecular Immunology and Immunogenetics Congress

March 20-21, 2017 Rome, Italy

Orly Avni

Faculty of Medicine in the Galilee, Bar-Ilan University, Israel

Scientific Tracks Abstracts: J Immunome Res

Abstract :

Dilated cardiomyopathy (DCM) is a life threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab-Christian-infants, ages 4-30 months from four families were diagnosed with DCM associated with mild skin, teeth and hair abnormalities. All passed away before age 3. A homozygous sequence variation creating a premature stop codon at PPP1R13L encoding the iASPP protein, was identified in three infants, and in the mother of the other two. Patients' fibroblasts and PPP1R13L-knocked down human fibroblasts presented higher expression levels of pro-inflammatory cytokine genes in response to lipopolysaccharide, as well as ppp1r13l-knocked down murine cardiomyocytes and hearts of ppp1r13l-deficient mice. The hypersensitivity to Lipopolysaccharide was NF-kB-dependent, and its inducible binding activity to promoters of pro-inflammatory cytokine genes was elevated in patients' fibroblasts. RNA-sequencing of ppp1r13l-knocked down murine cardiomyocytes and of hearts derived from different stages of DCM development in ppp1r13l-deficient mice revealed the crucial role of iASPP in dampening cardiac inflammatory response. Our results determined PPP1R13L as the gene underlying a novel autosomal recessive cardio cutaneous syndrome in humans, and strongly suggest that the fatal DCM during infancy is a consequence of failure to regulate transcriptional pathways necessary for tuning cardiac threshold response to common inflammatory stressors.

Biography :

Orly Avni is expert in gene regulation in the immune system. She has published many articles in reputed journals.

Email: Orly.Avni@biu.ac.il