The beta-thalassemia mutation spectrum in the Iranian population.

Beta-thalassemia is the most common hereditary disease in Iran. More than two million carriers of beta-thalassemia live in Iran. Since the Iranian population is a mixture of different ethnic groups, it is necessary to determine the frequency and distribution of mutations in the different parts of the country. For this purpose, we divided Iran in to eight different regions according to the geographic and ethnic distribution of the population. Over a 10-year period 1,217 beta-thalassemia chromosomes of 164 affected patients and 889 unrelated carriers were studied using the amplification refractory mutation system-polymerase chain reaction technique. We detected 81% beta-thalassemia mutations in the studied chromosomes. IVS-II-I (G --> A) was the predominant mutation found in our study (34%). Its relative frequency in the north was much higher than other regions, and it lessened toward the south, where the IVS-I-5 (G --> C) mutation was more common. IVS-I-5 (G --> C) (7.55%), codons 8/9 (+ G) (4.76%), and IVS-I-110 (G --> A) (4.76%) were the other most common mutations. The results presented here can be used as a basis of prenatal diagnosis of beta-thalassemia in different regions of Iran.

Analysis of a 43.6 kb deletion in a patient with Hunter syndrome (MPSII): identification of a fusion transcript including sequences from the gene W and the IDS gene.

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder. A novel mutation is described in an MPS II patient in whom the disorder is caused by a 43.6 kb deletion. Southern blot analysis, PCR analysis and subsequent sequencing of the deletion junction revealed that the deletion spans exons 1-7 of the iduronate-2-sulfatase (IDS) gene, the IDS-2 locus and exons 3-5 of the recently identified gene W. Short direct repeats of 12 bp were identified at both deletion breakpoints, suggesting that the deletion is the result of an illegitimate recombination event. A sequence motif (TGAGGA) which is identical to a consensus sequence frequently associated with deletions in man was identified at both breakpoints. This further supports the notion that this motif is a hot spot for recombination. Gene expression studies by RT-PCR analysis of total RNA derived from fibroblasts of the patient revealed the presence of a novel fusion transcript. DNA sequence analysis of the cDNA demonstrated that it consists of exons derived from both the gene W and the IDS gene. A similar but longer fusion transcript containing exons 2-4 of the gene W and exons 4-9 of the IDS gene could also be detected in RNA of normal cell lines originating from different tissues. This result further demonstrates the complex gene expression profile of the IDS region, which may contribute to the observed genomic instability of this region.

Supernumerary nipples in a Bartsocas-Papas patient in a consanguineous Iranian family.

We report a patient with Bartsocas-Papas syndrome surviving at 3 months. Our patient has supernumerary nipples in addition to the anomalies described previously in this syndrome.

Neu-Laxova syndrome: report of a case and comments.

We report on an infant with Neu-Laxova syndrome [Neu et al, 1971; Laxova et al, 1972; Povysilova et al, 1976; Lazjuk et al, 1979; Scott et al, 1981; Fitch et al, 1982; Mueller et al, 1983; Turkel et al, 1983; Paes et al, 1985], and emphasize the ichthyotic skin lesions as a prominent characteristic change in this syndrome and as the probable cause of some of the other findings. Also, we call attention to the increased fatty tissue beneath the epidermis and the atrophic muscles there embedded. These findings should be considered in the diagnosis of this syndrome.