Adrenomyeloneuropathy (AMN) represents a milder form of X-linked adrenoleukodystrophy (ALD), the most frequent peroxisomal disorder. The disease is characterised by an abnormal accumulation of saturated, very long chain, fatty acids, because of altered peroxisomal beta-oxidation that concomitantly leads to demyelination in the central and peripheral nervous systems. ALD shows a highly variable phenotypic expression and extensive mutation analysis in ALD patients has failed to establish a genotype-phenotype correlation, even in the presence of the same ALD-gene defect. Therefore, we have looked for a relationship between the molecular lesion and the age of onset in 19 patients with a well-classified clinical course of AMN. The nearly complete novel spectrum of ALD gene mutations identified has revealed no obvious correlation between the type of mutation and age of AMN onset in this small series. However, intrafamiliar concordance could be observed with respect to the occurrence of adrenocortical insufficiency. This supports the idea of one (or more) additional gene(s) contributing to the phenotypic expression of ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗

PubMedDate not supplied

Expression of CYP19 (aromatase) mRNA in different areas of the human brain.

The conversion of androgens to estrogens by CYP19 (cytochrome P450AROM, aromatase) is an important step in the mechanism of androgen action in the brain. CYP19 expression has been demonstrated in the brain of various animal species and in the human temporal lobe. Studies on postnatal CYP19 expression in various other areas of the human brain are rare and carried out in a limited number of post mortem obtained tissue. Therefore, we investigated CYP19 mRNA expression in fresh human frontal and hippocampal tissues and compared them to the expression in temporal neocortex tissues. We studied biopsy materials removed at neurosurgery from 45 women and 54 men with epilepsy. Quantification of CYP19 mRNA was achieved by nested competitive reverse transcription-PCR. CYP19 mRNA concentrations were significantly higher in temporal (2.29+/-0.40 arbitrary units, AU, mean +/- SEM; n = 57) than in frontal neocortex specimens (0.92+/-0.17 AU; n = 18; P<0.04). In hippocampal tissue specimens CYP19 expression (1.41+/-0.18 AU; n = 24) was lower than in temporal neocortex specimens, but the difference did not reach statistical significance. Sex differences were not observed in any of the brain regions under investigation. In conclusion, CYP19 mRNA is expressed in the human temporal and frontal neocortex as well as in the hippocampus. Regardless of sex, CYP19 expression was significantly higher in the temporal than in the frontal neocortex.

Adult↗

PubMedDate not supplied

Association of homozygous alpha-thalassaemia of the Southeast Asian type with hypospadias: still an intriguing enigma.

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Asia, Southeastern↗

PubMedDate not supplied

Diagnosis and monitoring of therapy of the various enzymatic defects causing congenital adrenal hyperplasia by semiautomatic capillary gas-liquid chromatography.

A semiautomatic capillary gas-liquid chromatographic method for the determination of urinary steroids has been developed. Trimethylsilylenol ethers were used as steroid derivatives instead of the more common methoxime trimethylsilyl ethers. The diagnosis of the various enzymatic defects causing congenital adrenal hyperplasia can be made using the characteristic pattern of urinary steroid chromatograms. Furthermore, the method presented can be used routinely to monitor therapeutic control in congenital adrenal hyperplasia. Reference data for patients of different age groups under good therapeutic control are presented.

3-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Female pseudohermaphroditism associated with a novel homozygous G-to-A (V370-to-M) substitution in the P-450 aromatase gene.

The conversion of C19 androgens to their corresponding C18 estrogens is catalyzed by an enzyme complex known as aromatase. P-450 aromatase is expressed in a tissue-specific manner and placental deficiency abolishes its function in protecting the female fetus from masculinization and the mother from prepartum virilization due to an excess of androgens. Here we report a novel homozygous aromatase mutation (Val370-to-Met) found in a girl with pseudohermaphroditism (Prader V). Sequence analysis showed the parents to be heterozygous for this amino acid substitution. Since P-450arom deficiency is a rare autosomally recessive transmitted disease, consanguinity in this kindred seemed to be obvious. With the characterization of four intragenic polymorphisms and subsequent haplotype analysis this assumption turned out to be most likely.

Aromatase↗