Acatalasia
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Several rare electrophoretic variants of red cell catalase were identified by Baur (1963). Nance et al. (1968) also described electrophoretic variants. Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
Wieacker et al. (1980) assigned a gene for catalase to 11p by study of man-mouse cell hybrid clones. In the hybrid cells, detection of human catalase was precluded by the complexity of the electrophoretic patterns resulting from interference by a catalase-modifying enzyme activity. Therefore, a specific antihuman antibody was used in conjunction with electrophoresis. In mouse, catalase is not syntenic to the beta-globin cluster or to LDH-A. Junien et al. (1980) investigated catalase gene dosage effects in a case of 11p13 deletion, a case of trisomy of all of 11p except 11p13, and a case of trisomy 11p13. The results were consistent with assignment of the catalase locus to 11p13 and its linkage with the WAGR complex (194070). Assay of catalase activity should be useful in identifying those cases of presumed new mutation aniridia that have a risk of Wilms tumor or gonadoblastoma, even in the absence of visible chromosomal deletion. In karyotypically normal patients with aniridia, Wilms tumor, or the combination of the two, Ferrell and Riccardi (1981) found normal catalase levels. Niikawa et al. (1982) confirmed the close linkage of catalase to the gene of the WAGR complex by demonstrating low levels of catalase activity in the erythrocytes of 2 unrelated patients with the WAGR syndrome and small deletions in 11p. From the study of dosage in 2 unrelated patients with an interstitial deletion involving 11p13, Narahara et al. (1984) concluded that both the catalase locus and the WAGR locus are situated in the chromosome segment 11p1306-p1305, with catalase distal to WAGR. Boyd et al. (1986) described a catalase RFLP with 2 different enzymes and used these polymorphisms to exclude deletion of the catalase gene in patients with sporadic aniridia, including one who was known to have a deletion and another suspected of having a deletion. Mannens et al. (1987) found deletion of the catalase locus in 6 of 9 patients with aniridia (AN2; 106210). One of these catalase-deficient aniridia patients had a normal karyotype. No catalase deletion could be demonstrated in 7 Wilms tumors. By classic linkage studies using RFLPs of the several genes as markers, Kittur et al. (1985) derived the following sequence of loci: cen-CAT–16 cM-CALC–8 cM-PTH-pter, with the interval between CAT and PTH estimated at 26 cM.
Differences in molecular weight of enzymes in different tissues is not proof that the enzymes are coded by different genes because tissue-specific variations in transcription or in posttranslational processing may occur. For example, catalase of red cells and that of liver are of different molecular weight, but from other evidence both are coded by the single gene located on 11p. Quan et al. (1986) found that the CAT gene is 34 kb long and split into 13 exons. Bell et al. (1986) gave the cDNA sequence for human kidney catalase. The coding region had 1,581 basepairs.
Acatalasia was first discovered in Japan by Takahara, an otolaryngologist who found that in cases of progressive oral gangrene, hydrogen peroxide applied to the ulcerated areas did not froth in the usual manner (Takahara and Miyamoto, 1948). Heterozygotes have an intermediate level of catalase in the blood. The frequency of the gene, although relatively high in Japan, is variable. The frequency of heterozygotes is 0.09 408852n Hiroshima and Nagasaki but is of the order of 1.4 408852n other parts of Japan (Hamilton et al., 1961). Acatalasia has been detected in Switzerland (Aebi et al., 1962) and in Israel (Szeinberg et al., 1963). In the Swiss and the Israelis, the homozygotes showed some residual catalase activity suggesting that this may be a different mutation from that responsible for the Japanese disease in which catalase activity is zero and no cross-reacting material has been identified. Hamilton and Neel (1963) presented evidence that at least 2 forms of acatalasia exist in Japan. In an extensive kindred with acatalasia in 2 sibships, heterozygotes showed catalase values overlapping with the normal. Ogata (1991) compared the properties of residual catalase in the Japanese and Swiss forms of the disease and in the mutant mouse. Hypocatalasia has also been found in the guinea pig, dog, and domestic fowl (see review by Lush, 1966). Shibata et al. (1967) found that an immunologically reactive but enzymatically inactive protein about one-sixth the size of active catalase is present in red cells of acatalasemics. In the acatalasemic mouse, Shaffer and Preston (1990) demonstrated that a CAG (glutamine)-to-CAT (histidine) transversion in the third position of codon 11 was responsible for the deficiency.
Allelic Variants:
.0001
ACATALASEMIA, JAPANESE TYPE
CAT, IVS4, G-A, +5
By sequencing the CAT gene for all exons, exon/intron junctions, and 5-prime and 3-prime flanking regions in a case of the Japanese type of acatalasemia, Wen et al. (1990) concluded that the genetic disorder resulted from a splicing mutation, namely, a G-to-A substitution at the fifth position of intron 4. In studies using chimeric genes constructed from the normal or mutant CAT gene and a part of the alpha-globin gene, Wen et al. (1990) showed that when the mutant gene construct was introduced into COS-7 cells, abnormal splicing occurred. The same splice site mutation was found in the genomic DNA of another unrelated acatalasemic person. Kishimoto et al. (1992) found the same mutation in 2 other unrelated Japanese patients and suggested that only a single mutated allele had spread in the Japanese population.
See Also:
Aebi et al. (1964); Aebi and Suter (1972); Agar et al. (1986); Feinstein et al. (1966); Kidd et al. (1987); Matsubara et al. (1967); Matsunaga et al. (1985); Quan et al. (1985); Schroeder and Saunders (1987)
References:
1. Aebi, H.; Baggiolini, M.; Dewald, B.; Lauber, E.; Sutter, H.; Micheli, A.; Frei, J.: Observations in two Swiss families with acatalasia. Enzym. Biol. Clin. 4: 121-151, 1964.