HLA-DQA1*01:181N, a Novel HLA-DQA1 Allele Identified by Next-Generation Sequencing.

Gain-of-function PDGFRA mutations, earlier reported in gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60 cases

HLA-B*40:01:83, carrying a single nucleotide substitution in exon 5 is described.

The novel allele HLA-DQB1*05:351 differs from DQB1*05:03:01:01 by a single nucleotide substitution in exon 3.

The HLA-C*07:1178 allele is characterised by a single nucleotide substitution in exon 6.

The HLA-C*07:01:130 allele differs from the HLA-C*07:01:01:01 allele by a single nucleotide substitution in exon 3.

The HLA-DRB1*03:218N allele differs from HLA-DRB1*03:174N by a single nucleotide substitution in exon 2.

A synonymous mutation in LMAN1 creates an ectopic splice donor site and causes combined deficiency of FV and FVIII

BACKGROUNDAutosomal dominant tubulointerstitial kidney disease (ADTKD) is a progressive chronic disease that is inherited in an autosomal dominant fashion. Symptoms include hyperuricemia, gout, interstitial nephritis, renal cysts, and progressive renal damage that can lead to end-stage renal disease. Mutations in the uromodulin gene (UMOD) characterize the ADTKD-UMOD clinical subtype of this disease. To date, > 100 UMOD mutations have been identified. Early diagnosis of ADTKD-UMOD is important to treat the disease, slow down disease progression, and facilitate the identification of potentially affected family members.CASE SUMMARYWe report a 40-year-old man harboring a novel heterozygous missense mutation in UMOD (c.554G>T; p. Arg185Leu). The patient had hyperuricemia, gout, and chronic kidney disease. The same mutation was detected in his daughter, aunt and cousin.CONCLUSIONA single nucleotide substitution in exon 3 of UMOD was responsible for the heterozygous missense mutation (c.554G>T, p.Arg185Leu).

Mannose-binding lectin (MBL) acts as a serum opsonin in innate immune defense and induces complement activation by the lectin pathway. In humans, low levels of functional serum MBL are caused by the dominant action of three single nucleotide substitutions in exon 1 that disrupt the glycine-rich backbone structure of the protein. The presence of common MBL variant alleles is associated with both infectious and autoimmune diseases. Conversely, it has also been suggested that MBL variants are maintained because of selective advantages for the host. In man, the MBL genetic system comprises one functional gene (MBL2) and one expressed pseudogene (MBL1P1), whereas the lower primate, the rhesus monkey resembles rodents with two functional MBL genes. We have investigated the molecular mechanisms behind the evolutionary loss of MBL expression from lower primates to man, including silencing of the MBL1P1 gene and the generation of MBL2 variant structural alleles and promoter polymorphisms leading to the present human MBL2 haplotypes. We present data showing that the MBL1P1 gene has been repeatedly hit throughout evolution and silenced eventually by mutations in the glycine residues of the collagen-like region. Our results indicate that the MBL1P1 gene has been selectively turned off during evolution through the same molecular mechanisms causing the MBL2 variant alleles in man, suggesting an evolutionary selection for low-producing MBL genes.

A single nucleotide substitution in exon 2 of HLA-C*06:02:01:01 results in the novel allele, HLA-C*06:391.

The HLA-DQA1*03:01:19 allele differs from HLA-DQA1*03:01:01:01 by a single nucleotide substitution in exon 3.

Mannose-binding lectin deficiency—revisited

Several new HLA-B locus alleles have been discovered in South American Amerindians. By contrast, analysis of the MHC class I alleles of North American native populations has revealed few new HLA-B alleles. This suggests that the HLA-B locus is evolving rapidly in South American populations. Here we describe the HLA-B locus alleles present in individuals from a Central American tribe, the Kuna of Panama. Using a sequence-based typing technique that separates alleles by denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing, we determined the HLA-B alleles from eight Kunas. Two of the HLA-B alleles present in the Kuna have been previously described in other South American Amerindian populations; one allele has been characterized in a Mexican-American. We characterized two new HLA-B alleles in the Kuna, HLA-B*3911 and HLA-B*5110. HLA-B*3911 differed from HLA-B*3905 by only a single nucleotide substitution in exon 3. This substitution resulted in an amino acid replacement of leucine by arginine at residue 156 in the alpha 2 domain. Such a change may affect the repertoire of peptides that are bound by this molecule. HLA-B*5110 differed significantly from other HLA-B*51 alleles in that it is the result of an unusually large intra-locus recombination event of minimally 216 nucleotides. This recombination results in an allele that is part HLA-B*51 and part HLA-B*40. Thus, more dramatic recombination events may also play a role in the rapid evolution of the HLA-B locus in Amerindians.

A single nucleotide substitution in exon 4 of HLA-A*32:01:01:01 results in novel HLA-A*32:148 allele.

A single nucleotide substitution in exon 3 of HLA-DQB1*06:03:01 results in a new allele, HLA-DQB1*06:03:27.