Novel and rare functional genomic variants in multiple autoimmune syndrome and Sjögren’s syndrome

• DOI: 10.1186/s12967-015-0525-x
• Publication Date: 2015-06-02T03:57:50Z
• Authors: Angad S Johar; Claudio Mastronardi; Adriana Rojas-Vil...; Hardip R Patel; Aaron Chuah; Kaiman Peng; Angela Higgins; Peter Milburn; Stephanie Palmer; Maria Fernanda Si...; Jorge I Velez; Dan Andrews; Matthew Field; Gavin Huttley; Chris Goodnow; Juan-Manuel Anaya; Mauricio Arcos-Bu...
• Keywords: Sjögren syndrome

Multiple autoimmune syndrome (MAS), an extreme phenotype of disorders, is a very well suited trait to tackle genomic variants these conditions. Whole exome sequencing (WES) widely used strategy for detection protein coding and splicing associated with inherited diseases. The DNA eight patients affected by MAS [all whom presenting Sjögren's (SS)], four SS alone 38 unaffected individuals, were subject WES. Filters identify novel rare functional (pathogenic–deleterious) homozygous and/or compound heterozygous in controls applied. Bioinformatics tools such as the Human gene connectome pathway network analysis applied test overrepresentation genes harbouring critical pathways networks involved autoimmunity. Eleven identified cases but not controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, FKRP. These subsequently their relatedness already autoimmunity was evaluated. Notably, LRP1/STAT6 mutation one patient another. disclosed strongest plausibility are extracellular intracellular anti-inflammatory that play key roles maintaining homeostasis immune system. Further; networks, pathways, interaction analyses showed LRP1 functionally related HLA-B IL10 it has substantial impact within immunological reaction bacterial other foreign proteins (phagocytosis, regulation phospholipase A2 activity, negative apoptosis response lipopolysaccharides). Further, ICA1 STAT6 also closely AIRE IRF5, two known genes. Novel exonic mutations may account identified. Among those, case being categorised potentially causative given presence intriguing patterns major shaping