Trisomy 21 as a sole acquired abnormality in an adult Omani patient with CD7- and CD9-positive acute myeloid leukemia.

We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American-British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed.

Hereditary thrombophilia in ethnic Omani patients.

Hereditary thrombophilias are a group of inherited conditions that predispose to thrombosis. Mutations like factor V Leiden, prothrombin gene variant 20210A, and hereditary hyperhomocysteinemia are associated with an increased risk for thromboembolism as compared to mutations in natural inhibitors of coagulation. There is also evidence that multiple defects co-exists in persons with a tendency for thrombosis. We studied prothrombotic determinants, namely protein C, protein S, and AT along with factor V Leiden (1691G-->A), prothrombin gene mutation (20210G-->A), CBS 844ins68 mutation, and MTHFR mutation (677C-->T) in consecutive ethnic Omani patients with first episode of a thrombophilic event, namely, deep vein thrombosis (DVT), and/or pulmonary embolism (PE) or thrombosis at an unusual site. Fasting plasma homocysteine was also analyzed. Factor V Leiden and the prothrombin gene mutation were not seen in any patient nor in any control subject studied. The thermolabile MTHFR mutation (677C-->T) was present in 14 patients (35.89%) whereas the CBS 844ins68 mutation was documented in 6 patients (15.38%); 3 patients were common in both groups. Six patients had low protein C (15.38%), two patients had low protein S (5.12%), but none had low AT levels. Interestingly, one patient had triple abnormality, namely, PC deficiency with both CBS 844ins68 mutation as well as the MTHFR mutation (677C-->T) whereas another two patients had the latter two mutations together. This data set, although small, reflects the importance of multiple screening strategies. The yield appears high, emphasizing the referral pattern to a tertiary health center. Of these patients, 43.58% had either or both the hyperhomocysteinemic mutations studied, whereas in 38.46% of these patients, no underlying cause for thrombophilia could be documented.

Heterozygous methylene tetrahydrofolate reductase mutation with mild hyperhomocysteinemia associated with deep vein thrombosis.

Hyperhomocysteinemia is known to be associated with arterial occlusive vascular disease and venous thrombosis. Here, we report a young ethnic Omani patient with recurrent venous thrombosis who was found to be heterozygous for 677C-T mutation in the methyltetrahydrofolate reductase (MTHFR) enzyme. Moderate hyperhomocystenemia was also observed, in the presence of normal red cell folate and serum B12 levels. No other documented marker of hereditary thrombophilia could be demonstrated in this patient, in spite of extensive investigation on multiple occasions.

Genotyping of the three major allelic variants of the human mannose-binding lectin gene by denaturing gradient gel electrophoresis.

The three major allelic variants of the mannose-binding lectin gene are responsible for structural defects leading to immune deficiency. The corresponding mutations are all located within exon 1 and result in amino acid substitutions in the collagenous region of the protein, which is involved in the oligomerization process. We have developed a simple and efficient strategy that permits simultaneous genotyping of these known allelic variants of the MBL gene by means of a single polymerase chain reaction (PCR) reaction followed by a denaturing gradient gel electrophoresis (DGGE). In addition, this procedure also allows for screening novel alleles due to mutations located elsewhere in the analyzed segment of the gene. During this study, we identified a previously undescribed nucleotide change in exon 1 at codon 44.

Prenatal diagnosis of beta-thalassaemia mutations using the reverse dot blot technique.

BACKGROUND: Beta-thalassaemia is the most common genetic disorder among Indians and a number of mutations causing this disease have been reported. Since effective treatment of thalassaemia major is complicated and very expensive, prenatal diagnosis has become an important option for those at risk of having an affected foetus. We report the use of a rapid hybridization method called 'reverse dot blot' for detection of specific mutations of the beta-globin gene. METHODS: DNA was obtained from a 12-week-old foetus by chorionic villus sampling and was amplified using specific primers by the polymerase chain reaction and analysed by the reverse dot blot test. Results were available within 36 hours after sampling. RESULT: The father and mother were found to be heterozygous for codon 15 (G-A) mutation of the beta-globin gene. The foetus was normal. CONCLUSION: Reverse dot blot is a rapid and reliable technique for mutation detection in the beta-globin gene and can be useful for antenatal diagnosis.