The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

In recent years many papers about diagnostic applications of diffusion tensor imaging (DTI) have been published. This is because DTI allows to evaluate in vivo and in a non-invasive way the process of diffusion of water molecules in biological tissues. However, the simplified description of the diffusion process assumed in DTI does not permit to completely map the complex underlying cellular components and structures, which hinder and restrict the diffusion of water molecules. These limitations can be partially overcome by means of diffusion kurtosis imaging (DKI). The aim of this paper is the description of the theory of DKI, a new topic of growing interest in radiology. DKI is a higher order diffusion model that is a straightforward extension of the DTI model. Here, we analyze the physics underlying this method, we report our MRI acquisition protocol with the preprocessing pipeline used and the DKI parametric maps obtained on a 1.5 T scanner, and we review the most relevant clinical applications of this technique in various neurological diseases.

Three of four children in a family have homozygous (less than 1% of normal) deficiency of factor H of the complement system and both parents, who are first cousins, are heterozygous for the same defect. The father and two of the H-deficient siblings also have a partial C2 deficiency. One of the children with combined deficiencies is affected by systemic lupus erythematosus with nephritis. No increased susceptibility to infections has been observed in the family. H deficiency is inherited in an autosomal codominant manner and is independently transmitted from C2 deficiency and HLA haplotypes. In the homozygous state it is associated with very low serum concentrations of B and C3, barely demonstrable as activated molecules. C5 is greatly reduced (less than 5%). Also, properdin and C6-9 are decreased. The findings in this family demonstrate that the occurrence of systemic lupus erythematosus in one of the children affected by a combined deficiency of factor H and C2 raises the question whether this pathology is related to the complete factor H or to the heterozygous C2 deficiency. Complete H deficiency is not necessarily accompanied by overt illness.

A total of 100 Chinese blood donors (50 from Shen-Zhen and 50 from Taiwan) were studied by the participants in addition to 9 reference samples. A new nomenclature for the CR1 structural alleles was recommended by the participants which would use a numbering system, e.g. CR1*1. The structural allele frequencies in the Chinese were: CR1*1 (190 kD) 0.96, CR1*2 (220 kD) 0.03, CR1*3 (160 kD) 0.01 and CR1*4 (250 kD) 0.00. The HindIII expression polymorphism was also studied and the high expressing allele had a gene frequency of 0.71 while the low expressor gene frequency was 0.28. Erythrocyte copy numbers were quantified and compared between laboratories with good correlation (R = 0.55–0.88). The mean (± SD) erythrocyte copy number was 463 (± 229) in the Taiwan donors and 446 (± 207) in the Mainland Chinese.

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