A rare case of a boy with de novo microduplication at 5q35.2q35.3 from central Brazil.

Genomic disorders are genetic diseases that are caused by rearrangements of chromosomal material via deletions, duplications, and inversions of unique genomic segments at specific regions. Such rearrangements could result from recurrent non-allelic homologous recombination between low copy repeats. In cases where the breakpoints flank the low copy repeats, deletion of chromosomal segments is often followed by reciprocal duplication. Variations in genomic copy number manifest differently, with duplication and deletions of the same genomic region showing opposite phenotypes. Sotos syndrome is caused by alterations in the dosage of NSD1 on human chromosome 5 by either deletions or mutations, such as microdeletion of 5q35.2q35.3. In general, patients carrying reciprocal microduplication at 5q35.2q35.3 present no clinical phenotype or milder phenotype than do patients with microdeletion at the same locus. We report the first case of 5q35.2q35.3 microduplication encompassing NSD1 in a patient from central Brazil. We identified a genomic imbalance corresponding to a de novo 0.45 Mb microduplication at 5q35.2q35.3 by chromosomal microarray analysis and study of low-copy repeats. The proband had microduplication in the chromosomal region containing NSD1, which resulted in a Sotos syndrome reversed phenotype, and this duplication was associated with microcephaly, short stature, and developmental delay. Analysis of the genomic structure of the rearranged 5q35.2q35.3 chromosomal region revealed two major low-copy repeat families, which caused the recurrent rearrangements. Chromosomal microarray analysis is a potential tool to identify microrearrangements and guide medical diagnosis, which has to be followed by a non-directive genetic counseling approach to improve the quality of life of the patient.

Effects of glycerol and sorbitol on the thermal dependence of the lysis of human erythrocytes by ethanol.

In this work, the effects of 1 mol/L glycerol or sorbitol on the thermal dependence (27-47 degrees C) of the lysis of human erythrocytes by ethanol in saline solution (0.154 mol/L NaCl) have been evaluated. Lysis was monitored by measurement of the absorbance at 540 nm. Ethanol produced either lysis or protection against lysis depending on the conditions. These antagonistic effects are attributed to the existence of expanded (R) and compacted (T) erythrocytes, present under conditions of low and high osmolarity, respectively. The transitions of lysis of the R state and formation and lysis of the T state were all found to be sigmoidally defined. The ethanol concentration at the midpoint of the lysis transition of the R state (D(50R)) was found to decrease with increasing temperature and osmolarity. In the presence of glycerol or sorbitol, an increase in temperature led to smaller decreases in D(50R) and osmotic protection against lysis. The ethanol concentration at the midpoint of formation (S(50T)) and lysis (D(50T)) of the T state also decreased with increasing temperature and osmolarity. Lysis of R state erythrocytes is determined by the chaotropic action of ethanol, but the formation and lysis of T state erythrocytes are determined by osmotic pressure effects.