Document Detail

Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II.
MedLine Citation:
PMID:  7718898     Owner:  NLM     Status:  MEDLINE    
Recessive congenital methemoglobinemia (RCM) due to NADH-cytochrome b5 reductase (cytb5r) deficiency leads to two different types of diseases. In the type I form, cyanosis is the only symptom, and the soluble enzyme is defective in red blood cells. In the type II form, cyanosis is associated with severe mental retardation and neurologic impairment; the enzymatic defect is systemic, involving both soluble and membrane-bound isoforms. We characterized mutations responsible for cytb5r deficiency in three unrelated patients with severe RCM type II. The first patient presented a homozygous exon 5 skipping. The only mutation detected was a homozygous G to C transversion at position +8, downstream from the 5' splice site of exon 5. We suggest that this unusual mutation might be responsible for the abnormal splicing of the primary transcripts, resulting in frameshift with premature STOP codon. The second mutation found corresponds to a homozygous C to T transition changing the Arg-218 codon to a premature STOP codon in exon 8. The third case was a compound heterozygote, carrying two different mutant alleles in the cyb5r gene. One allele presented a missense mutation with replacement of Cys-203 (TGC) by Arg (CGC) in exon 7. The second allele carried a 3-bp deletion (TGA) of nucleotides 815 to 817, modifying two contiguous codons in exon 9 of the cDNA with loss of Met-272. These results confirm the genetic polymorphism of cytb5r gene mutations identified in RCM type II, as observed for the mutations described in the RCM type I, and shed light on the molecular bases of the two different diseases associated with cytb5r deficiency.
L M Vieira; J C Kaplan; A Kahn; A Leroux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood     Volume:  85     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-05-25     Completed Date:  1995-05-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2254-62     Citation Subset:  AIM; IM    
Institut Cochin de Génétique Moléculaire, INSERM U129, Paris, France.
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MeSH Terms
Amino Acid Sequence
Base Sequence
Binding Sites
Codon / genetics
Cytochrome Reductases / deficiency,  genetics*
Cytochrome-B(5) Reductase
DNA Mutational Analysis
DNA, Complementary / genetics
Exons / genetics
Flavin-Adenine Dinucleotide / metabolism
Genes, Recessive
Introns / genetics
Methemoglobinemia / classification,  genetics*
Molecular Sequence Data
NAD / metabolism
Point Mutation
Polymerase Chain Reaction
Polymorphism, Genetic
Protein Conformation
Sequence Deletion
Reg. No./Substance:
0/Codon; 0/DNA, Complementary; 146-14-5/Flavin-Adenine Dinucleotide; 53-84-9/NAD; EC 1.6.2.-/Cytochrome Reductases; EC Reductase

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