Hemochromatosis and pyruvate kinase deficiency

Braekeleer, Marc De; St-Pierre, C.; Vigneault, Anne; Simard, Hervé; Médicis, Eveline de

doi:10.1007/bf01703147

Cited by 11 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the other patient (case 9), splenectomy performed at the age of 12 resulted in a progressive increase of serum ferritin up to 20-fold the baseline in 6 years, associated with grade 4 siderosis at liver biopsy. These observations confirm the need to monitor iron status in PK-deficient patients, particularly in those who have been splenectomized or who have coincidental heterozygosity for idiopathic haemochromatosis (De Braekeleer et al, 1991;Zanella et al, 1993).…”

Section: Discussionsupporting

confidence: 70%

Molecular characterization of the PK‐LR gene in sixteen pyruvate kinase‐deficient patients

et al. 2001

View full text Add to dashboard Cite

We studied the PK‐LR gene in 16 unrelated patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase deficiency. Fifteen different mutations were detected among the 28 mutated alleles identified: two deletions (del 1010G, del 1042–1044); one four nucleotide duplication (nt 1515–1518, GGTC); one splice site [IVS6(−2)t]; nine missense (991A, 1003A, 1151T, 1160G, 1181T, 1181A, 1456T, 1483A, 1529A); and two nonsense (721T, 1675T) mutations. Eight of them [del 1010G, del 1042–1044, dupl 1515–1518, IVS6(−2)t, 1003A, 1160G, 1181T, 1181A] were novel. The deletion 1042–1044 causes the loss of Lys 348. Deletion 1010G and duplication 1515–1518 determine a frameshift and the creation of a stop codon at nucleotides 1019 and 1554 respectively. Mutation IVS6(−2)t leads to an alteration of the 5′ and 3′ splice site consensus sequence; the cDNA analysis shows a 67‐bp deletion in the first part of exon 11 (del 1437–1503). All the four new missense mutations involve highly conserved amino acids. The most frequent mutation in Italy would appear to be 1456T. Correlation was made between mutations, biochemical characteristics of the enzyme and clinical course of the disease.

show abstract

Section: Discussionsupporting

confidence: 70%

Molecular characterization of the PK‐LR gene in sixteen pyruvate kinase‐deficient patients

et al. 2001

View full text Add to dashboard Cite

show abstract

“…Several hereditary disorders have been shown to have a high frequency in the French Canadian population of Saguenay Lac-Saint-Jean, a geographically isolated region located 200 km north-east of Quebec City and surrounded by tracts of unsettled land and forest. 13,16 The values of the mean inbreeding and kinship coefficients were much…”

Section: Discussionmentioning

confidence: 99%

Juvenile hemochromatosis locus maps to chromosome 1q in a French Canadian population

Rivard

Lanzara

Grimard³

et al. 2003

Eur J Hum Genet

View full text Add to dashboard Cite

Juvenile hemochromatosis (JH) is a rare autosomal recessive disorder that causes iron overload. In the French Canadian region of Saguenay Lac-Saint-Jean the worldwide largest cohort of JH cases has been identified. Here, we report the mapping of this large cohort of cases to the HFE2 locus on chromosome 1q. A maximum multipoint location score of 7.02 was observed with marker D1S2344. A common ancestral haplotype, showing the presence of a founder effect, was identified. The analysis of recombinants allowed us to confirm the JH candidate region.

show abstract

“…Usually the degree of iron overload correlates with the administration of iron, i.e. with the number of transfusions given, but case reports have documented patients with concurrent hemochromatosis, in whom iron overload is present despite few or no transfusions (57)(58)(59). In one case report where HFE genotype data were available, one of two brothers with sideroblastic anemia had the HFE genotype C282YjH63D; his body iron stores were twice those of his brother, who carried no HFE mutations (57).…”

Section: Interaction Between Hh and Other Genetic Disordersmentioning

confidence: 99%

Hemochromatosis: genetics helps to define a multifactorial disease

1998

View full text Add to dashboard Cite

Hereditary hemochromatosis (HH) is a common autosomal recessive disorder that can result in iron overload and a wide range of clinical complications, including hepatic cirrhosis, diabetes mellitus, hypopituitarism, hypogonadism, arthritis, and cardiomyopathy. People with HH can be detected at an asymptomatic stage of the disease by abnormalities in serum iron measures. Early detection is desirable, because periodic phlebotomy provides effective treatment for iron overload and may prevent complications of the disorder. The natural history of HH is poorly understood, however, and the proportion of people detected by screening who will develop serious complications of HH is unknown. The genetics of HH may help to resolve these questions. The gene, HFE, and two mutations, C282Y and H63D, have been identified; the C282Y mutation has a higher penetrance than the H63D mutation, and appears to result in a greater loss of HFE protein function. Most people with HH are C282Y homozygotes, a small proportion are compound heterozygotes or H63D homozygotes, and some have no identifiable HFE mutation or are HFE heterozygotes, suggesting that additional mutations associated with HH are yet to be found. Gender and environmental agents, such as alcohol and dietary iron, influence phenotypic expression of HH. The severity of HH is thus determined by an interaction between genotype and modifying factors. HFE mutations also appear to increase the likelihood of iron overload in inherited anemias and to promote the clinical manifestations of porphyria cutanea tarda. HH is an important paradigm for medical genetics because it offers an opportunity to explore the complexity of gene–gene and gene–environment interactions.

show abstract

Hemochromatosis and pyruvate kinase deficiency

Cited by 11 publications

References 7 publications

Molecular characterization of the PK‐LR gene in sixteen pyruvate kinase‐deficient patients

Molecular characterization of the PK‐LR gene in sixteen pyruvate kinase‐deficient patients

Juvenile hemochromatosis locus maps to chromosome 1q in a French Canadian population

Hemochromatosis: genetics helps to define a multifactorial disease

Contact Info

Product

Resources

About