Most humans harbor both CD177neg and CD177pos neutrophils but 1–10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1), which appears to have resulted from allelic gene conversion. In CD177 expressing individuals the CD177 locus contains both CD177P1 and CD177 sequences. The proportion of CD177hi neutrophils in the blood is a heritable trait. Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed. Human neutrophil heterogeneity for CD177 expression arises by ectopic allelic conversion. Resolution of the genetic basis of CD177null phenotype identifies a method for screening for individuals at risk of CD177 isoimmunisation.

We report a germline nonsense mutation within the extracellular domain of the RING finger ubiquitin ligase RNF43, segregating with a severe form of serrated polyposis within a kindred. The finding provides evidence that inherited RNF43 mutations define a familial cancer syndrome.Human Genome Variation (2015) 2, 15013; doi:10.1038/hgv.2015.13; published online 16 April 2015The serrated polyposis syndrome comprises multiple epithelial polyps in the colon and rectum of serrated histology. WHO clinical criteria 1 are the presence of 420 serrated polyps throughout the colon, or 45 proximal to the rectum. Serrated polyps, particularly large sessile polyps in the proximal colon, frequently exhibit the oncogenic V600E mutation together with hypermethylation of the mismatch repair protein MLH1 and are responsible for 15-20% of sporadic colorectal cancer (CRC).

Acute (1 h) atorvastatin administration is highly hepatoprotective against IRI in NASH, fatty and lean livers. Key mechanisms include suppression of inflammation by prevention of NF-κB activation, microvascular protection via eNOS activation and suppression of TXB2 and MP release. Short-term intravenous statin treatment is a readily available and effective preventive agent against hepatic IRI, irrespective of obesity and fatty liver disease, and merits clinical trials in at-risk patients.

We present a case of a 21-year-old male diagnosed with difficult to treat idiopathic thrombocytopenia and autoimmune haemolytic anaemia at the age of 14. He initially improved with high doses of oral prednisone however relapsed at the age of 16, requiring multiple immunosuppressive agents, intravenous immunoglobulins (IVIG), splenectomy and Eltrombopag to induce remission. He was noted to have hypogammaglobulinemia and low memory B cells, however ongoing IVIG therapy precluded vaccine studies and functional antibody deficit could not be demonstrated.Five years later he presented to hospital with bilateral sixth nerve palsies, raised intracranial pressure and new, widespread lymphadenopathy. An inguinal lymph node biopsy revealed non-caseating granulomas. Although there was an initial resolution of ocular symptoms with high doses of prednisone, our patient re-presented 3 weeks later with bilateral lower limb weakness and several falls. MRI spine imaging revealed symmetrical granulomatous inflammation in the nerve roots of the cauda equina. Reexamination of the inguinal lymph node with further immunochemistry analysis revealed intact lymphoid tissue architecture and presence of plasma cells.Sarcoidosis is an idiopathic, multi-system disorder that is characterised by non-caseating granulomas that are histologically indistinguishable from the lesions present in the granulomatous variant of common variable immunodeficiency. As the clinical features of the two disorders can also significantly overlap, the presence of plasma cells and normal architecture in the lymph node can be helpful in making the diagnosis. We discuss a rare case of neurosarcoidosis involving the peripheral nervous system and further outline diagnostic and management dilemmas. Background: Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder associated with immune deficiency and cancer susceptibility caused by a defect in the ataxia-telangiectasia mutated (ATM) gene resulting in impaired DNA repair. Lymphoma and leukaemia is the most commonly associated malignancy with childhood AT.