Array-CGH study of partial trisomy 9p without mental retardation

Partial trisomy 9p is one of the most common detected autosomal structural anomalies, so the phenotype-genotype correlation of this rearrangement has been well described. Despite variation in size of the 9p duplications, trisomy 9p syndrome is characterized by typical dysmorphic features and a variable but constant psychomotor and mental retardation. Previously reported phenotype genotype correlation studies proposed that the critical region for phenotype is located in 9p22. We report here on a new patient with partial trisomy 9p13.3→9pter in an 8-year-old boy with typical trisomy 9p dysmorphic features but a normal mental development. Cytogenetics investigations showed that our patient karyotype was 47,XY,+ der(22)t(9;22)(p13.q11) inherited by a 3:1 disjunction of a maternal reciprocal translocation t(9;22)(p13.q11). FISH and array CGH analysis were used to better characterize duplicated chromosomal regions and showed a large duplication of chromosome 9p13.3→9pter associated to microduplication in 22q11.1. The size of the duplications in chromosomes 9p and 22q were estimated about 33.9 and 2.67 Mb, respectively. The comparison between this case and those reported in the literature allows us to support that all syndromes show variability and that not all partial trisomies 9p are associated with intellectual disability.     

Molecular characterization of a discrete hemoglobinopathy upon investigation for a lung hydatic cyst in an old Tunisian patient

We report the case of an old Tunisian patient hospitalized for a complicated hydatic cyst of the right lung. Primary laboratory investigation showed a microcytic hypochromic anemia with an abnormal hemoglobin pattern. Hemoglobin analysis and DNA sequencing of the β-globin gene revealed a compound heterozygote, HbO-Arab/cd 39 β°-thalassemia. This hemoglobinopathy was never diagnosed earlier. It spent undiagnosed until the patient presented with hydatic cyst. Coexistence of the two pathologies complicated the general state of the patient and led to a severe anemia. The patient has undergone a surgical therapy for the hydatic cyst and was advised to start a follow up for her hemoglobinopathy.     

Molecular analysis of HumDN1 VNTR polymorphism of the human deoxyribonuclease I in systemic lupus erythematosus

Deoxyribonuclease I (DNASE1) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of systemic lupus erythematosus (SLE). The purpose of this study was to screen DNASE1 gene for mutations that may have an effect on susceptibility to develop SLE. DNA was extracted from 76 Kuwaiti SLE patients and 92 race-matched controls. PCR-direct sequencing was used to screen DNASE1 promoter, coding sequence and exon–intron boundaries for mutation. Association of genomic variations was assessed using a Chi-square test. Molecular analysis of the DNASE1 gene did not reveal any mutation. However, a 56-bp repeat was detected in intron4 which was previously reported and named HumDN1. The allelic and genotypic distributions of the HumDN1 VNTR were compared between SLE patients and healthy subjects. Alleles were denoted as 2, 3, 4, 5 and 6 corresponding to the number of repeats of the 56 bp unit. Alleles 4, 5, and 6 showed significant association with SLE. Allele 5 showed the highest association [χ² = 32.57; P ≤ 0.001; OR = 4.16; 95% CI: (2.55–6.79)]. Association of allele 5 was also found at the genotypic level, where genotype 5/5 is more prevalent in SLE subjects as compared with controls (17% versus 9%). We report a significant association of HumDN1 VNTR polymorphism in DNASE1 gene with SLE. Further functional assays needed to assess the effect of this VNTR on DNASE1 activity and its association with SLE.