Interleukin 10 gene promoter polymorphism and risk of diffuse large B cell lymphoma [DLBCL]

Given the importance of understanding the genetic variations involved in the pathogenesis of non-Hodgkin's lymphoma [NHL], this work was designed to study the impact of IL-10 [-1082 G/A; rs!800896 and -819 C/T; rs!800871] gene promoter polymorphism on susceptibility of Egyptians to diffuse large B cell lymphoma [DLBCL]; the major type of NHL. To the best of our knowledge, this study is the first one that examines IL-10 promoter polymorphism in DLBCL in Egyptians. Genotyping polymorphism is performed using sequence-specific primers polymerase chain reaction [SSP-PCR] in 100 Egyptian DLBCL patients and 119 normal controls. Circulating plasma levels of IL-10 were measured using Enzyme-linked immunosorbent assay [ELISA]. Insignificant change in IL-10 [-1082 and -819] genotypes was recorded. Although A allele is slightly decreased in DLBCL patients, it did not reach statistical significance. GT haplotype was significantly elevated [P < 0.05] in NHL patients. A significant linkage disequilibrium between the -1082 and 819 SNPs with D' = 0.596 and r[2] = 0.1032 [P < 0.001] was demonstrated. Significantly increased plasma IL-10 [P < 0.01] was found which is positively correlated [r = 0.307; P < 0.01] with the disease Taken together, our findings demonstrated that IL-10 promoter gene polymorphism [-1082 and -819] may not have an influence on the clinical outcome of DLBCL, especially in terms of overall secretion level. Further investigations of other cytokine gene polymorphisms will lead to a better understanding of the disease's biological background

Genetic study of multiple congenital contractures [Arthrogryposis Multiplex Congenita]

This work was carried out to study different conditions with arthrogryposis and their mode of inheritance that would allow proper diagnosis, management and appropriate genetic counseling. The study included 30 patients with arthrogryposis attending the Genetic Clinic, Medical Research Institute, Alexandria University. The frequency of parental consanguinity was 50%. An abnormal pregnancy history was found in 22 cases. Both upper and lower limb affections were noticed in twenty-eight patients, while isolated upper limb affection occurred in one case and isolated lower limb affection in one case. Finger joints were the most commonly affected. It was concluded that the examination of all joints in the upper and lower limbs is the key of diagnosis in the majority of cases of arthrogryposis. There is a marked inter- and intra-familial variability in many conditions with arthrogryposis. An accurate diagnosis is important in genetic counseling, prevention, management and prognosis

High resolution banding technique in detection of minimal residual disease in acute myeloid leukemia

A significant proportion of patients with acute myeloid leukemia who achieve remission subsequently experience frank relapse of their disease, and their ultimate prognosis is typically poor. Investigation of minimal residual disease has proven to be a valuable tool for predicting impending relapse before clinical and hematologic manifestations. The aim of this study was the detection of minimal residual disease in AML patients fallowing complete remission [CR] using high resolution chromosome banding technique of bone marrow specimens and their implication on clinical course of the disease. The present study included 27 patients with de novo AML as initial series. Their diagnosis was based on morphological and immunophenotypical criteria. Among these, 15 patients [55.5%] achieved morphologic complete remission, whom the present study was done on that cases for one year of follow up for detection of relapse; 3 patients were M1, 5 were M2, 2 were M3, 2 were M4 and 3 were M5. High resolution banding technique of bone marrow cells revealed that seven patients [7/15; 47%] had cytogenetic abnormalities; 3 had chromosomal translocations [t[6;9], t[15;17], t[l;8]], one with chromosome 5 monosomy, one deletion [del [7q]], one chromosome duplication [dup [13q]] and one with trisomy 8. During the follow up period, 71% [5/7] of cases with cytogenetic abnormalities relapsed, while 37.5% [3/8] of cases with normal cytogenetics relapsed. There was a significant difference between those who relapsed and had cytogenetic abnormalities and those who relapsed and had normal cytogenetics in their response to treatment. In conclusion, high resolution chromosome banding technique of bone marrow cells is valuable in the detection of minimal residual disease in AML and therefore patients at high risk of relapse could be identified for better management

Detection of microdeletions involving the DAZ locus in idiopathic male infertility

Deletions of the AZFc [azoospermic factor c] region of the Y chromosome including DAZ gene are the most common known cause of spermatogenic failure. This study was conducted with the aim of detecting Y chromosome microdeletions involving the DAZ locus in idiopathic male infertility to allow rapid and accurate diagnosis required for proper genetic counseling. The study included 30 male patients with idiopathic azoospermia [24/30] or oligozoospermia [6/30]. A control group consisted of 10 normal fertile males and 5 females. All cases were subjected to detailed history, clinical examination, assessment of testicular volume, semen analysis, serum hormonal profile [FSH, LH, testosterone], testicular biopsy, chromosome analysis, polymerase chain reaction [PCR] amplification of two specific loci of the DAZ gene on the Y chromosome [sY254 and sY255], single strand conformations polymorphism analysis [SSCP]. The result of the study revealed that deletions involving the sY245 and sY255 DAZ loci were found in 4 cases [4/30; 13.3%]; 3 azoospermic patients and one with severe oligozoospermia. All four cases with microdeletions had decreased testicular volume, normal serum LH and T, serum FSH was elevated in 3 of them and normal in one. The two loci were amplified normally in the male control group and failed to amplify in the female control group. SSCP analysis failed to find any point mutations in sY254 and sY255 in patients with absence of microdeletions of DAZ gene. In conclusion, the estimated frequency of microdeletions involving the DAZ locus is 13.3% in azoospermic and severely oligozoospermic Egyptian men with idiopathic infertility. Polymerase chain reaction amplification of the DAZ locus is a rapid and accurate method for the diagnosis of microdeletions of the Y chromosome in patients with idiopathic infertility especially those seeking micromanipulation assisted reproduction

Neural tube defects: sex ratios and recurrence risk

This study included fifty families having sixty-four patients with neural tube detects [NTD]. Fourteen families had two affected members and thirty-six ones had only one affected member. The common types of NTD as well as the relation between the position of the NTD lesions and sex were studied. Also, the sex ratio and the concordance for NTD lesion and sex were estimated. The recurrence rate in sibs of the probands was also calculated. Anencephaly was found in 60.9% of cases, followed by encephalocele in 18.8%, then meningomyelocele in 12.5% and finally the spina bifida in 7.8%. The overall male/female ratio was 1.06. A male preponderance was observed in the anencephalic patients, while female excess was found in the encephalocelic group. In lower spina bifida, all cases were males. Concordance of sex was found in 75% of the upper lesions and in 100% of the lower ones. The recurrence rate was high in the upper lesions. Periconceptional vitamins and folic acid as well as proper prenatal diagnosis by both anatomical and biochemical evaluations of the fetus have reduced the recurrence of the NTD

Pericentric inversion of chromosome 9 and clinical significance

The clinical significance of pericentric inversion of chromosome 9 [P inv [9]] cases was studied retrospectively from 680 peripheral blood cultures collected over a three- year period. The cytogenetic studies revealed 12 subjects with P inv [9]. Peripheral blood cultures were performed using the microtechnique. Chromosome examination was done using G-banding technique for all cases and C-banding technique was further done for carriers of P inv [9]. The clinical presentation of the inversion carrier cases was mental retardation in four cases and in one of these cases, the inversion was familial. Three partners of couples with repeated spontaneous abortion were also carriers of the inversion. One case had trisomy 21 in association with P inv [9], while another carrier of the inversion had a nephew with trisomy 21. One case had dysmorphic features and one case had a history of subfertility among the mother's family

Relationship between head circumference and psychomotor development in down syndrome

In the present study, the head circumference of 44 Down syndrome patients as well as 80 control subjects was measured and plotted on the Egyptian control chart. Assessment of the psychomotor skills of Down syndrome patients and the control group was performed using the Denver development screening test. The developmental quotient was calculated. The head circumference of DS patients was significantly lower than the control group. The head circumference of Down syndrome patients showed deviation from the normal population range with advancing age. The gross motor sector showed the most severe delay in all ages studied. The language sector showed a decline with age and was the most retarded domain in the older Down syndrome patients. An intermediate +ve, though insignificant correlation, was found between the head circumference and the developmental quotient in Down syndrome patients aged 6 months - 1.5 years, while a strong +ve correlation between the head circumference and the developmental quotient was found in Down syndrome patients aged 1.5 - 2.5 years, implying that the head circumference plays a role in the psychomotor retardation of Down syndrome patients

Autosomal chromosome aberrations among children with severe mental retardation

Over a 4 year period, 240 children with severe mental retardation were evaluated cytogenetically. Their ages ranged from 2-11 years. Peripheral blood cultures were performed using the microtechnique. Chromosome examination was done using G-banding technique. Cytogenetic studies identified 63 [26.25%] cases with abnormal karyotypes including 55. Down syndrome; 51 standard and 4 translocated Down syndrome, 1 trisomy 18, 11 cases had structural autosomal aberrations; 10 unbalanced and 1 balanced, 4 had autosomal deletion, 2 had extrachromosomal material. The study revealed the need for an increased awareness to order chromosome analysis in those individuals with severe mental retardation