Infevers (Internet Fevers; http://fmf.igh.cnrs.fr/ISSAID/infevers), a website dedicated to mutations responsible for hereditary autoinflammatory diseases, was created in 2002 and has continued to evolve. This new version includes eight genes; six were already present: MEFV, MVK, TNFRSF1A, NLRP3, NOD2, PSTPIP1, and two are new, LPIN2 and NLRP7. Currently, Infevers contains over 540 sequence variants. Several new database functions were recently instituted. The website now accepts confidential data and complex alleles. For each gene, a newly created menu offers: 1) a tabular list of the variants that can be sorted by several parameters; 2) a gene graph providing a schematic representation of the variants along the gene; 3) statistical analysis of the data according to the phenotype, alteration type, and location of the mutation in the gene; 4) the cDNA and gDNA sequences of each gene, showing the nucleotide changes along the sequence, with a color‐based code highlighting the gene domains, the first ATG, and the termination codon; and 5) a “download” menu making all tables and figures available for the users, which, except for the gene graphs, are all automatically generated and updated upon submission of the variants. Finally, the entire database was curated to comply with the HUGO Gene Nomenclature Committee (HGNC) and HGVS nomenclature guidelines, and wherever necessary, an informative note was provided. Infevers has already proven useful for the scientific community with a mean number of visits per month of 200 in 2002 and 800 in 2007, and its new design will lead to a more comprehensive comparative analysis and interpretation of auto‐inflammatory sequence variants. Hum Mutat 29(6), 803–808, 2008. Published 2008, Wiley‐Liss, Inc.

We previously mapped a maternal locus responsible for biparental complete hydatidiform moles (BiCHMs) to 19q13.4. The two index patients had a total of 14 molar pregnancies, eight abortions at various developmental stages, and one 16-year-old healthy offspring. We suggested that the defective gene deregulates the expression of imprinted genes. Here, we report the methylation status of four imprinted genes in two BiCHMs from the two sisters, the 16-year-old normal offspring, and two sporadic BiCHMs from unrelated patients. Using two bisulfite-based methods, we demonstrate a general trend of abnormal hypomethylation at the paternally expressed genes, PEG3 and SNRPN, and hypermethylation at the maternally expressed genes, NESP55 and H19, in two to four BiCHMs. Using single nucleotide polymorphisms, we provide the first evidence that SNRPN, NESP55 and H19 are abnormally methylated on the maternal alleles in BiCHMs. We show, in the BiCHMs from the two sisters, that the abnormally methylated H19 allele is inherited from either the maternal grandmother or the maternal grandfather. These data suggest that the abnormal methylation in BiCHMs is not due to an error in erasing the parental imprinting marks but rather in the re-establishment of the new maternal marks during oogenesis or their postzygotic maintenance. The defective 19q13.4 locus may have led to the development of variable degrees of ‘faulty’ paternal marks on the maternal chromosomes.

Hydatidiform mole (HM) is the product of an aberrant human pregnancy in which there is an abnormal embryonic development and proliferation of placental villi. The incidence of HM varies between ethnic groups, and occurs in 1 in every 1500 pregnancies in the USA. All HM cases are sporadic, except for extremely rare familial cases. The exact mechanisms leading to molar pregnancies are unknown. We previously postulated that women with recurrent hydatidiform moles are homozygous for an autosomal recessive defective gene. To map this gene genetically, we initiated a genome-wide scan with highly polymorphic short tandem repeats in individuals from two families with recurrent HM. Here, we demonstrate that a defective maternal gene is responsible for recurrent HM. This gene resides on chromosome 19q13.3–13.4 in a 15.2 cM interval flanked by D19S924 and D19S890. The identification of a gene for HM adds new insights into the molecular genetics of early embryogenesis and may be relevant to the large number of patients with sporadic HM.