ABSTRACT
Myotonic Dystrophy type I [DM1] the most common form of muscular dystrophy in adults affecting 1/800 individuals is a dominantly inherited disorder with a multi-systemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of a trinucleotide [CTG] repeat in the 3 untranslated region of the myotonic dystrophy protein kinase [DMPK] gene located on choromosome 19q13.3. The normal copy number is 5-37 CTG repeat whereas it is expanded in DM1 patients and the expansion size broadly correlates with the severity of the symptoms. The aim of this study was to determine the clinical and genetic characteristic of DM1 in Iranian patients for genotype-phenotype correlation methods. Clinical assessment was based on the muscular disability rating scale [MDRS] and a sum of symptoms score [SSS]. Molecular analysis [PCR and Southern blot] was used to clarify uncertain clinical diagnoses and confirm the clinical findings. Forty six patients from twenty five DM1 families were reviewed. In all the DM1 patients, the wide clinical symptoms confirmed the reported phenotypic vaiability of disorder. The range of CTG expansion of the mutated allele was 97-833 CTG repeats and an inverse correlation between age of onest and repeat length was observed. A clear relation between the size of the CTG repeat and the clinical disease score [MDRS] was found but not with SSS. No correlation was seen between the endocrine dysfunction and the expansion size in DM1 patients
ABSTRACT
Thalassemia is one of the most common hemoglobin disorders, in which alpha-thalassemia appears in affected individuals with hypochromic microcytic anemia. Because of the absence of the mutation detection capabilities in the most health care centers in Iran, the most patients with alpha-thalassemia misdiagnosed as beta silent carriers. Until now, no inclusive research has been done to expose the patterns of it in Khuzestan. Therefore, in the present study we decided to clarify the prevalence of the mutations in alpha -Thalassemia in Khuzestan. One hundred and fourteen patients from Khuzestan were selected among the patients, referred to Kariminejad and Najmabadi Pathology and Genetics Center, between 1998-2006, showing the signs of hypochromic microcytic anemia and normal HbA2 levels. First of all, they were all tested for 3 common alpha -thalassemia mutations,-3.7, -4.2, --MED, by gap-PCR amplification method. Alpha-Globin Strip Assay of the nine mutation panel and DNA sequencing was used to determine other major contributes in Khuzestan. We could detect alpha -thalassemia mutations for 84.2% of tested individuals. 79.2% had cis-type alpha -thalassemia, 13.5% trans-type and 7.3% was a carrier for two cis-type mutations. In total, 72.9% were silent carrier, 19.8% alpha -thalassemia trait, and 7.3% had alpha -thalassemia major. As an early report 27.4% of the tested alleles were found to be mutated. The - alpha[3.7] single gene deletion was the most frequent alpha -globin mutation in our population representing 55.2% of alpha -thalassemia mutations in Khuzestan. Twelve other mutations [--MED, alpha[PA2[GAA]], - alpha[4.2], alpha[cd19], alpha[-5nt], alpha[cd14], alpha[PA1[AAG]], alpha[CS], anti 3.7 triplication, alpha[St], alpha[cd21], alpha[cd59]. We strongly recommend screening for the identified ten common mutations to improve the molecular diagnosis of anemia