Gene: [22q133/DIA1] diaphorase 1 (NADH) (cytochrome b-5 reductase); methemoglobinemia (cytochrome b-5 reductase deficiency);

GEN

[1] The gene length is 30.5 kb. Exons: 9 (21, 132, 73, 107, 130, 84, 86, 100, and 171 bp); introns: 8 (12238, 5235, 382, 2580, 458, 212, 3384, and 3792 bp). All of them meet the <5'-GT..AG-3'> frame criterion (Sharp PA: Cell, 23, 643-646, 1981); they are characterized by a high content of Alu-repeats, 17 complete and 12 incomplete ones (e.g., there are nine repeats in intron 1, four of them forming a tandem); deletions up to 1.5 kb in length are frequent in this region.
[2] The 5'-nts region, about 0.5 kb in length, does not contain the canonical TATA and CCAAT promoters, however, it is rich in GGGCGG regions, which are probably binding sites for transcriptional factor Sp1 (Gidoni &: Nature, 312, 409-413, 1984); in addition, this region fits the criterion of Bird (Bird &: Nature, 321, 209-213, 1986) for a ; the 3'-utl region (958 bp) does not contain the canonical signal of polyadenylation, however, an AGTAAA region, which may serve as a poly(A) signal, is located at suitable distance (14 bp upstream) from the poly(A) site."

FAG

[1] Biochemical genetic studies revealed four diaphorase isoforms; all are registered in MIM Catalogue: DIA1 (MIM:250800), DIA2 (MIM:125870), DIA3 (MIM:125880), and DIA4 (MIM:125860).
[2] Only two genes have been mapped definitely and included in HGM. These are DIA1 (GEM:22q133/DIA1) and DIA4 (GEM:16q221/NMOR1); both have been designated in HGM as 'cytochrome b5 reductase'. Attempts to map DIA2 (GEM:00.0/DIA2) did not give conclusive results."

PAT

At least two types of cytochrome b5 reductase deficiency are distinguished: the erythrocytic one (type I, the DIA1 deficiency occurs in red blood cells only) and the generalized type (type II). In clinically more severe type II, the DIA1 deficiency is found in many cells besides red blood cells and is accompanied by mental retardation and neurological disturbances."

REF

CLO,LOC,MOL "Bull PC &: Ann Hum Genet, 52, (Part 4), 263-268, 1988
LOC,CYG "Fisher RA &: Ann Hum Genet, 41, 151-155, 1977
REV,PAT "Gibson QH: Am J Hematol, 42, 3-6, 1993
LOC,CYG "Hors-Cayla MC &: Hum Genet, 58, 140-143, 1981
MAP "Julier C &: AJHG, 42, 297-308, 1988
PND "Junien C &: Prenatal Diag, 1, 17-24, 1981
LOC,CYG "Junien C &: Hum Genet, 42, 233-239, 1978
PND "Kaftory A &: Isr J Med Sci, 22, 837-840, 1986
MUT,PAT "Katsube T &: AJHG, 48, 799-808, 1991
MUT,PAT "Kobayashi Y &: Blood, 75, 1408-1413, 1990
MUT,PAT "Shirabe K &: AJHG, 57, 302-310, 1995
MUT,PAT "Shirabe K &: JBC, 269, 5952-5957, 1994
GEN,SEQ,EXP "Tomatsu S &: Gene, 80, 353-361, 1989
MUT,PAT "Vieira LM &: Blood, 85, 2254-2262, 1995
CLO,SEQ,PAT "Yubisui T &: PNAS, 84, N11, 3609-3613, 1987
SEQ,MOP,PEP "Yubisui T &: J Biochem, 99, 407-422, 1986
SEQ,MOP,PEP "Yubisui T &: J Biochem, 96, 579-582, 1984

KEY

hem, xen, lip

CLA

coding, basic

LOC

22 q13.3

MIM

MIM: 250800

EZN

ENZYME: 1.6.2.2

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