First Report of a Derivative Chromosome 13 with a Duplicated 11p15 Locus Associated with Silver-Russell Syndrome.

Silver-Russell Syndrome (SRS) is a disorder that is primarily characterised by intrauterine growth restriction which may occur asymmetrically or in whole, leading to a fetus being small relative to its gestational age. We present a female infant (proband) born in 2018 at a tertiary hospital in Muscat, Oman, with severe congenital anomalies. The proband carried a >25Mb duplication of the chromosomal 11p15-11pter locus of chromosome 13; creating a derivative chromosome 13 (der[13]) and was reported as 46,XX,der(13)add(11p15-11pter). A methylation-sensitive assay confirmed a diagnosis of SRS. Although the prognosis for SRS patients is generally good, the proband presented with a clinically severe phenotype culminating in death at the age of nine months. To the best of the authors' knowledge, this is the first report of a derivative chromosome 13 with a duplicated 11p15 locus in a patient with SRS.

Importance of FISH combined with Morphology, Immunophenotype and Cytogenetic Analysis of Childhood/ Adult Acute Lymphoblastic Leukemia in Omani Patients.

Genetic changes associated with acute lymphoblastic leukemia (ALL) provide very important diagnostic and prognostic information with a direct impact on patient management. Detection of chromosome abnormalities by conventional cytogenetics combined with fluorescence in situ hybridization (FISH) play a very significant role in assessing risk stratification. Identification of specific chromosome abnormalities has led to the recognition of genetic subgroups based on reciprocal translocations, deletions and modal number in B or T-cell ALL. In the last twelve years 102 newly diagnosed childhood/adult ALL bone marrow samples were analysed for chromosomal abnormalities with conventional G-banding, and FISH (selected cases) using specific probes in our hospital. G-banded karyotype analysis found clonal numerical and/or structural chromosomal aberrations in 74.2% of cases. Patients with pseudodiploidy represented the most frequent group (38.7%) followed by high hyperdiploidy group (12.9%), low hyperdiploidy group (9.7%), hypodiploidy (<46) group (9.7%) and high hypertriploidy group (3.2%). The highest observed numerical chromosomal alteration was high hyperdiploidy (12.9%) with abnormal karyotypes while abnormal 12p (7.5%) was the highest observed structural abnormality followed by t(12;21)(p13.3;q22) resulting in ETV6/RUNX1 fusion (5.4%) and t(9;22)(q34.1;q11.2) resulting in BCR/ABL1 fusion (4.3%). Interestingly, we identified 16 cases with rare and complex structural aberrations. Application of the FISH technique produced major improvements in the sensitivity and accuracy of cytogenetic analysis with ALL patients. In conclusion it confirmed heterogeneity of ALL by identifying various recurrent chromosomal aberrations along with non-specific rearrangements and their association with specific immunophenotypes. This study pool is representative of paediatric/adult ALL patients in Oman.

Simplified method for the collection, storage, and comet assay analysis of DNA damage in whole blood.

Single-cell gel electrophoresis (comet assay) is one of the most common methods used to measure oxidatively damaged DNA in peripheral blood mononuclear cells (PBMC), as a biomarker of oxidative stress in vivo. However, storage, extraction, and assay workup of blood samples are associated with a risk of artifactual formation of damage. Previous reports using this approach to study DNA damage in PBMC have, for the most part, required the isolation of PBMC before immediate analysis or freezing in cryopreservative. This is very time-consuming and a significant drain on human resources. Here, we report the successful storage of whole blood in ~250 µl volumes, at -80°C, without cryopreservative, for up to 1 month without artifactual formation of DNA damage. Furthermore, this blood is amenable for direct use in both the alkaline and the enzyme-modified comet assay, without the need for prior isolation of PBMC. In contrast, storage of larger volumes (e.g., 5 ml) of whole blood leads to an increase in damage with longer term storage even at -80°C, unless a cryopreservative is present. Our "small volume" approach may be suitable for archived blood samples, facilitating analysis of biobanks when prior isolation of PBMC has not been performed.

Cytogenetic studies in couples with recurrent miscarriage in the Sultanate of Oman.

Miscarriage, defined as spontaneous pregnancy loss at <20-28 weeks' gestation, is a common clinical problem. Balanced chromosomal rearrangements in either parent are an important cause of repeated pregnancy loss, particularly in the first trimester. In this study, chromosomal abnormalities that cause recurrent miscarriage were evaluated in Omani parents and some of their dysmorphic children. A total of 380 couples (760 individuals) with two or more recurrent miscarriages were examined for chromosomal aberrations during the period 1999-2006. For each proband the chromosomal preparations were analysed and karyotyped after applying a Giemsa-trypsin banding method. The overall incidence of chromosomal anomaly was 26 out of 760 individuals (3.42%). These abnormalities included 21 (2.8%) structural aberrations and 5 (0.7%) numerical anomalies. In addition to these abnormalities, 39 (5.1%) chromosomal variants were also found. The nature of these abnormalities and their relation to obstetric history are discussed. In conclusion, chromosomal abnormality is one of the causes of recurrent miscarriage. This study illustrates the incidence and distribution of chromosomal abnormalities among Omani couples with recurrent miscarriage. Cytogenetic findings could provide valuable information for genetic counselling and allow monitoring of future pregnancies by prenatal diagnosis in couples with a history of recurrent miscarriage.

Incidence of chromosome abnormalities in the Sultanate of Oman.

OBJECTIVES: To evaluate the cytogenetic findings in Omani children referred for suspected chromosomal anomalies that caused a variety of clinical disorders. Secondly, to study the frequency of chromosomal abnormalities in these patients and to compare our results with those reported elsewhere. METHODS: We performed chromosomal analysis on 1800 consecutive pediatric patients referred to the Cytogenetics section between June 1999 and May 2004 at Central Public Health Laboratories, Sultanate of Oman. Indication for referrals for exclusion of chromosomal rearrangements was multiple congenital anomalies, dysmorphic features, unclassified mental retardation, developmental delay, growth, and endocrine disorders. We carried out the lymphocyte culture according to standard methods. RESULTS: We found various types of chromosomal anomalies in 510 (28.3%) children and showed abnormal karyotypes in the form of trisomy 21 (391; 21.7%), trisomy 18 (32; 1.8%), trisomy 13 (20; 1.1%), sex chromosome aberrations (50; 2.8%) and other types of abnormalities (17; 0.95%). There was a considerable phenotypic-cytogenetic heterogeneity. We found a high rate of chromosomal abnormalities in the present study, and we observed variations in the frequency of chromosomal aberrations reported by different investigators. CONCLUSION: The higher incidence of the chromosomal abnormalities demonstrates the importance of cytogenetic evaluation in patients with dysmorphic features and congenital anomalies. Our findings suggest that chromosome analysis is a useful tool in the investigation of children with genetic disorders of unknown origin for confirmation of clinical diagnosis and proper medical care followed by genetic counseling and management.