Characterization of a Novel Mutation in the NADH-Cytochrome b5 Reductase Gene Responsible for Rare Hereditary Methaemoglobinaemia Type I

2013 ◽  
Vol 130 (2) ◽  
pp. 122-125 ◽  
Author(s):  
Katarzyna Rawa ◽  
Liliana Chelmecka-Hanusiewicz ◽  
Danuta Plochocka ◽  
Katarzyna Pawinska-Wasikowska ◽  
Walentyna Balwierz ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Cytochrome B5 ◽  
Type I ◽  
Cytochrome B5 Reductase ◽  
Reductase Gene ◽  
Nadh Cytochrome

A novel G143D mutation in the NADH-cytochrome b5 reductase gene in an Indian patient with type I recessive hereditary methemoglobinemia

2008 ◽  
Vol 40 (3) ◽  
pp. 323-327 ◽  
Author(s):  
Prabhakar S. Kedar ◽  
Prashant Warang ◽  
Anita H. Nadkarni ◽  
Roshan B. Colah ◽  
Kanjaksha Ghosh
Keyword(s):  
Cytochrome B5 ◽  
Type I ◽  
Indian Patient ◽  
Cytochrome B5 Reductase ◽  
Reductase Gene ◽  
Nadh Cytochrome

Compound heterozygosity of two missense mutations in the NADH-cytochrome b5 reductase gene of a Polish patient with type I recessive congenital methaemoglobinaemia

2003 ◽  
Vol 70 (6) ◽  
pp. 404-409 ◽  
Author(s):  
Dorota Grabowska ◽  
Danuta Plochocka ◽  
Ewa Jablonska-Skwiecinska ◽  
Anna Chelstowska ◽  
Irmina Lewandowska ◽  
...  
Keyword(s):  
Cytochrome B5 ◽  
Type I ◽  
Missense Mutations ◽  
Compound Heterozygosity ◽  
Cytochrome B5 Reductase ◽  
Reductase Gene ◽  
Nadh Cytochrome ◽  
Polish Patient

Congenital methaemoglobinaemia Type I in a Turkish infant due to a novel mutation, Pro144Ser, in NADH-cytochrome b5 reductase

2004 ◽  
Vol 5 (4) ◽  
pp. 367-370 ◽  
Author(s):  
Melanie J Percy ◽  
Hale Oren ◽  
Geraldine Savage ◽  
Gülersu Irken
Keyword(s):  
Novel Mutation ◽  
Cytochrome B5 ◽  
Type I ◽  
Cytochrome B5 Reductase ◽  
Nadh Cytochrome

scholarly journals Four new mutations in the NADH-cytochrome b5 reductase gene from patients with recessive congenital methemoglobinemia type II

Blood ◽  
1995 ◽  
Vol 85 (8) ◽  
pp. 2254-2262 ◽  
Author(s):  
LM Vieira ◽  
JC Kaplan ◽  
A Kahn ◽  
A Leroux
Keyword(s):  
Stop Codon ◽  
Cytochrome B5 ◽  
Premature Stop Codon ◽  
Gene Mutations ◽  
Type I ◽  
Type Ii ◽  
Cytochrome B5 Reductase ◽  
Reductase Gene ◽  
Membrane Bound ◽  
Nadh Cytochrome

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.

scholarly journals Familial Congenital Methemoglobinemia in Pomeranian Dogs Caused by a Missense Variant in the NADH-Cytochrome B5 Reductase Gene

2018 ◽  
Vol 32 (1) ◽  
pp. 165-171 ◽  
Author(s):  
H. Shino ◽  
Y. Otsuka-Yamasaki ◽  
T. Sato ◽  
K. Ooi ◽  
O. Inanami ◽  
...  
Keyword(s):  
Cytochrome B5 ◽  
Missense Variant ◽  
Cytochrome B5 Reductase ◽  
Reductase Gene ◽  
Nadh Cytochrome

A novel mutation in the NADH-cytochrome b5 reductase gene of a Chinese patient with recessive congenital methemoglobinemia

Blood ◽  
2000 ◽  
Vol 95 (10) ◽  
pp. 3250-3255 ◽  
Author(s):  
Yao Wang ◽  
Yu-Shui Wu ◽  
Pei-Zhen Zheng ◽  
Wen-Xi Yang ◽  
Guo-An Fang ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Novel Mutation ◽  
Cytochrome B5 ◽  
Clinical Manifestations ◽  
Mutant Enzyme ◽  
Chinese Family ◽  
Coding Region ◽  
Cytochrome B5 Reductase ◽  
Nadh Cytochrome

Abstract Recessive congenital methemoglobinemia due to nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase (b5R) deficiency is classified into 2 clinical types: type 1 (erythrocyte type) and type 2 (generalized type). We found a Chinese family with type 1 recessive congenital methemoglobinemia, the patients from which were diagnosed according to clinical symptoms and b5R enzyme activity in the blood cells. To learn the molecular basis of type 1 recessive congenital methemoglobinemia in this Chinese family, we isolated total RNA from the peripheral leukocytes of the propositus and b5R complementary DNA (cDNA) by reverse transcription– polymerase chain reaction (RT-PCR). The coding region of the b5R cDNA was analyzed by sequencing the cloned PCR products. The results showed that the propositus was homozygous for a G→A transition at codon 203 in exon 7, changing a cysteine to a tyrosine (Cys203Tyr). To characterize the mutant enzyme, both glutathione S-transferase (GST)-fused wild-type b5R and GST-fused mutant Cys203Tyr b5R were expressed in Escherichia coli and affinity purified. The results showed that the catalytic activity of the enzyme was not much affected by this amino acid substitution, but the mutant enzyme exhibited decreased heat stability and increased susceptibility to trypsin. These properties of the mutant enzyme would account for the restricted b5R deficiency and mild clinical manifestations of these type 1 patients. The finding of this novel mutation makes codon 203 the only position within the b5R gene at which more than 1 mutation has been found.

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