[Surveying SMN gene deletions in Iranian patients with spinal muscular atrophy and prenatal diagnosis]

Spinal muscular atrophy is a group of alpha-motor neuron. There are three genes for this disorder, of which SMN with two copies centromeric and telomeric is the most important one. In 95% of SMA patient's telomeric copy of SMN is homozygously deleted and the remaining has point mutation in this gene. In most of the patient's, exon 7 and 8 of SMN 1 is deleted. Therefore, analysis of SMN1 mutation is very important for carrier detection. The aim of this study was analysis of SMN1 mutation and determination of its frequency among Iranian patients. After genetic counseling and estimation of clinical symptoms of patients based on SMA consortium, molecular analysis based on PCR-RFLP has been performed. Frequency of consanguineous marriage in our study was 60%, while most of the patients were come from central and northern part of Iran. Of 243 families, 195 were categorized as type I, 30 as type II, and 18 as type III. Analysis of exon 7 deletion among families with live affected child showed that 94% of families with SMA type I, 95% in type II families and 100% in SMA type III had homozygous deletion. In prenatal diagnosis, twenty one of ninety two [22.8%] fetal samples were found to be affected and these pregnancies were terminated. The frequency of homozygous deletion of exon 7 of SMN1 was 94%. This is in agreement with Western Europe, China, Japan, and Kuwait

[ investigation of Duchenne muscular dystrophy deletions in Iranian families and prenatal diagnosis]

Duchenne muscular dystrophy [DMD] is one of the most common X-linked genetic disorders, commonly seen in children. It is caused by mutations in Dystrophin gene and clinically manifests with severe muscle weakness and eventually leads to death in the second or third decades of life. In the absence of an appropriate cure, prenatal diagnosis [PND] appears to be the best approach to reduce the burden of the disease on the individual family and ultimately on the society. During the last five years, prenatal diagnosis was offered on request to 85 families, having one or more affected male children. Initially, the deletions in the DMD gene were identified by Multiplex PCR, screening for 20 exons. Then, three intragenic RFLPs [PERT 87-15lBamH1, PERT87-8ITaq1, PERT 87- 151XmnI] and two main CA repeats [5'- DYS and 3' DYS microsatellite analysis] that have-been shown to be highly heterozygous in the previous studies, were used to perform carrier detection and linkage analysis. Deletions were found in 43 affected boys [50.6%]. Most of the deletions were found in exons 49 and 50. However, there were not any mutations identified in the promoter region. In 42 families these three intragenic RFLPs were utilized and in 26 of them one or more RFLPs were informative [61.9%]. In 30 families two microsatellite repeat analysis were done to identify the mutant alleles and in 12 families, 5'-Dys was informative. Prenatal diagnosis was performed in 25 families [16 CVS cases and 9 amnion cases]. The cases were 14 male fetuses [5 cases affected, 9 cases not affected] and 11 female fetuses [4 cases were carriers and the remaining cases were normal]. Therefore, it is concluded that multiplex PCR technology and linkage analysis, can be used effectively for PND and carrier detection in Iran