title: Pseudodominant inheritance of the hyperimmunoglobulinemia D with periodic fever syndrome in a mother and her two monozygotic twins.
abstract: Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is a recessively inherited recurrent fever syndrome. We describe a family of 2 monozygotic twins and their mother with characteristic symptoms of HIDS, but normal levels of IgD and IgA, and with a dominant inheritance pattern. Mevalonate kinase (MK) activity was deficient in both children, and analysis of the MVK gene revealed compound heterozygosity for 2 new mutations, G25G and R277H. Being positioned adjacent to a donor splice site, the G25G mutation was shown by reverse transcription-polymerase chain reaction analyses to cause aberrant splicing of the MVK messenger RNA, thus being disease-relevant. The mother, who was also symptomatic during her childhood and adolescence, was a compound heterozygote for I268T and R277H. Our findings expand the genetic and ethnic spectrum of HIDS and show that the possible presence of this disease cannot be excluded based solely on inheritance patterns. In each case in which HIDS is clinically suspected, analysis of MK activity and/or the MVK gene (especially exons 9 and 11) should be performed.
authors.affiliation: Department of Pediatric Rheumatology, Children's Hospital, Olgahospital, Bismarckstrasse 8, D-70176 Stuttgart, Germany. a.hospach@olgahospital.de
authors.forename: Toni
authors.initials: T
authors.lastname: Hospach
authors.forename: Pia
authors.initials: P
authors.lastname: Lohse
authors.forename: Helmut
authors.initials: H
authors.lastname: Heilbronner
authors.forename: Guenther E
authors.initials: GE
authors.lastname: Dannecker
authors.forename: Peter
authors.initials: P
authors.lastname: Lohse
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D002675:Child, Preschool; D004200:Diseases in Twins / Q000201:enzymology / Q000235:genetics*; D005076:Exanthema / Q000473:pathology; D010505:Familial Mediterranean Fever / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005334:Fever / Q000473:pathology; D005799:Genes, Dominant; D006801:Humans; D006942:Hypergammaglobulinemia / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D007072:Immunoglobulin D / Q000032:analysis*; D008969:Molecular Sequence Data; D009035:Mothers; D009154:Mutation; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014430:Twins, Monozygotic
chemical_list: D007072:Immunoglobulin D; D012333:RNA, Messenger; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase