Detection of cryptic telomeric chromosomal abnormalities in children with idiopathic mental retardation by fluorescence in situ hybridization [FISH]

The cause of mental retardation, present in approximately 3% of school age children is unexplained in the majority of cases. Cryptic rearrangements involving the telomeres [the distal ends of chromosomes] are thought to account for a substantial number of patients with unexplained mental retardation and multiple congenital anomalies, although the exact incidence of these rearrangements is still unclear. With the advent of chromosome-specific telomeric probes and the use of fluorescence in situ hybridization [FISH], it is now possible to identify submicroscopic rearrangements of the distal ends of chromosomes that may otherwise go undetected using conventional cytogenetic studies. A group of 25 children with idiopathic mental retardation [IQ < 70] and their parents have been investigated to determine the frequency of submicroscopic telomeric rearrangements associated with idiopathic mental retardation. Fifteen healthy children [IQ >70] served as a control group. We have detected two cryptic telomeric abnormalities among children with idiopathic mental retardation. The mother of proband 1 has been found to have cryptic abnormality while the parents of proband 2 were found to have normal chromosomes, suggesting that cryptic subtelomevic rearrangements may be inherited or may be de novo mutation. This study describes a sensitive approach to the diagnosis of cryptic abnormalities between the G band negative ends of chromosomes and confirms the significant contribution of cryptic telomeric rearrangements to idiopathic mental retardation

Oral fluids as risk factors for intrafamilial transmission of hepatitis C virus

To evaluate the frequency of hepatitis C virus [HCV] infection among the family members of chronically infected HCV patients, to investigate the oral cavity fluids as a possible risk factor for transmission of HCV infection, to asses the reliability of gingival crevicular fluid [GCF] and saliva anti-HCV [HCVAb] and HCV-RNA testing for detection of HCV and to study the oral mucosa and periodontal condition of HCV infected subjects. Serum, GCF and saliva specimens were obtained from 19 index cases with chronic HCV and their relatives [n = 83] to detect HCVAb by ELISA and HCV-RNA by a modified commercial polymerase chain reaction [PCR] assay. The clinical oral mucosal and periodontal conditions were evaluated. HCV infection was detected in the relatives of 17 out of 19 families. The newly diagnosed cases were 41%, of them 66.7% were parents, 34.6% brothers and 4.8% sisters. The intrafamilial frequency of positive anti-HCV was 60.8%, 47.1% and 38.2% in the serum, GCF and saliva specimens respectively of the total studied population. HCV-RNA was detected in 52%, 41.2% and 28.4% in the same body fluids in order of frequency. The sensitivity and specificity for anti-HCV in the serum, GCF and saliva were 100%, 90.6%, 71.7% and 81.6%, 100%, 98% respectively. The corresponding values for HCV-RNA were 100%, 79.2%, 54.7% and 100%, 100%, 100% respectively. Strong positive associations were found between serum PCR and anti-HCV testing in serum, GCF, saliva and HCV-RNA testing in GCF and saliva [P<0.001]. No significant difference was found regarding mucosal and periodontal clinical evaluation between HCV positive and negative persons. It was concluded that: [1] The relatives of HCV infected patients are at risk to acquire the disease. [2] GCF and saliva presented detectable levels of anti-HCV and HCV-RNA, which might be sources of HCV infection among family members. [3] Detectable levels of GCF and saliva anti-HCV and HCV-RNA may be of diagnostic value in HCV infection. [4] No correlation was found between oral mucosa and periodontal condition and HCV infection

HLA gene polymorphism and susceptibility for stroke in children with sickle cell anemia

Stroke occurs in 8-10% of children with Sickle Cell anemia [SCA] and is a major cause of morbidity. Prevention of first stroke would be preferable because even one stroke can cause irreversible brain injury. The association of HLA type with stroke provides the first evidence of a multigenic involvement in a specific manifestation of SCA. We investigated eleven children with SCA with magnetic resonance imaging [MRI] abnormalities consistent with cerebral infarcts [group I] and fourteen asymptomatic children with SCA with normal MRI scans [group II] to determine whether HLA type was associated with risk of stroke with SCA. Comparison, of the results of HLA typing between the SCA patients with a positive and those with a negative MRI revealed significant difference in distribution of alleles at the class II loci. For DRB1, the DR3 alleles, DRB1*0301and*0302 appeared to be associated with susceptibility to stroke. The DR15 alleles, DRB1* 1501 and 1503, were protective for stroke. For the DQB1 locus, DQB1 0201 was associated with stroke, while DQB1*0602 appeared protective. Documentation of an association between HLA alleles and risk of stroke in patients with SCA suggests that HLA system plays a role in the pathophysiology of vascular changes leading to stroke