|Classification and genetic features of neonatal haemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism.|
|PMID: 11546828 Owner: NLM Status: MEDLINE|
|Neonatal haemochromatosis (NH) is a severe and newly recognised syndrome of uncertain aetiology, characterised by congenital cirrhosis or fulminant hepatitis and widespread tissue iron deposition. NH occurs in the context of maternal disease including viral infection, as a complication of metabolic disease in the fetus, and sporadically or recurrently, without overt cause, in sibs. Although an underlying genetic basis for NH has been suspected, no test is available for predictive analysis in at risk pregnancies. As a first step towards an understanding of the putative genetic basis for neonatal haemochromatosis, we have conducted a systematic study of the mode of transmission of this disorder in a total of 40 infants born to 27 families. We have moreover carried out a molecular analysis of candidate genes (beta(2)-microglobulin, HFE, and haem oxygenases 1 and 2) implicated in iron metabolism. No pathogenic mutations in these genes were identified that segregate consistently with the disease phenotype in multiplex pedigrees. However, excluding four pedigrees with clear evidence of maternal infection associated with NH, a pedigree showing transmission of maternal antinuclear factor and ribonucleoprotein antibodies to the affected infants, and two families with possible matrilineal inheritance of disease in maternal half sibs, a large subgroup of the affected pedigrees point to the inheritance of an autosomal recessive trait. This included 14 pedigrees with affected and unaffected infants and a single pedigree where all four affected infants were the sole offspring of consanguineous but otherwise healthy parents. We thus report three distinct patterns of disease transmission in neonatal haemochromatosis. In the differentiation of a large subgroup showing transmission of disease in a manner suggesting autosomal recessive inheritance, we also provide the basis for further genome wide studies to define chromosomal determinants of iron storage disease in the newborn.|
|A L Kelly; P W Lunt; F Rodrigues; P J Berry; D M Flynn; P J McKiernan; D A Kelly; G Mieli-Vergani; T M Cox|
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|Type: Case Reports; Journal Article; Research Support, Non-U.S. Gov't|
|Title: Journal of medical genetics Volume: 38 ISSN: 1468-6244 ISO Abbreviation: J. Med. Genet. Publication Date: 2001 Sep|
|Created Date: 2001-09-07 Completed Date: 2002-01-10 Revised Date: 2009-11-18|
Medline Journal Info:
|Nlm Unique ID: 2985087R Medline TA: J Med Genet Country: England|
|Languages: eng Pagination: 599-610 Citation Subset: IM|
|Department of Medicine, University of Cambridge, Level 5, Box 157, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.|
|APA/MLA Format Download EndNote Download BibTex|
Extrachromosomal Inheritance / genetics
HLA Antigens / genetics
Haplotypes / genetics
Heme Oxygenase (Decyclizing) / genetics
Hemochromatosis / congenital*, genetics*, metabolism, physiopathology
Histocompatibility Antigens Class I / genetics
Iron / metabolism*
Liver Failure / congenital*, genetics*, metabolism, physiopathology
Maternal-Fetal Exchange / immunology
Pregnancy Complications, Infectious / immunology, metabolism, microbiology, virology
beta 2-Microglobulin / genetics
|0/HFE protein, human; 0/HLA Antigens; 0/HLA-F protein, human; 0/Histocompatibility Antigens Class I; 0/Membrane Proteins; 0/beta 2-Microglobulin; 7439-89-6/Iron; EC 188.8.131.52/HMOX1 protein, human; EC 184.108.40.206/Heme Oxygenase (Decyclizing); EC 220.127.116.11/Heme Oxygenase-1; EC 18.104.22.168/heme oxygenase-2|
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