Journal of Pediatric Genetics - Volume 3, issue 1

Authors: Dutta, Usha R.

Article Type: Review Article

Abstract: Chromosomal aberrations are a major cause of human genetic diseases. Conventional cytogenetic banding techniques are the method of identification for both numerical and structural chromosomal abnormalities but with limited resolution. However, precise identification and characterization of the chromosomal abnormalities can only be achieved by advanced molecular cytogenetic techniques. These techniques are based mainly on fluorescence in situ hybridization, which have become an invaluable tool in the field of diagnostics. The advent of these molecular cytogenetic techniques has helped in the identification of chromosomal abnormalities to its minutest level. Apparently, the leads in molecular cytogenetic techniques have paved way for advanced …molecular diagnosis, which now plays a significant role in both diagnostics and clinical research. These advances have led to the increased knowledge of the possible molecular mechanism involved in the chromosomal rearrangements and the genotype-phenotype correlation thus helping the patients towards better diagnosis and genetic counseling. This article highlights the advances in molecular cytogenetic techniques emphasizing the precision in identification of chromosomal rearrangements, and also illustrates few chromosomal abnormalities pediatric cases identified using these molecular cytogenetic techniques. Show more

Keywords: Molecular cytogenetic techniques, FISH, SKY, array CGH, MLPA

DOI: 10.3233/PGE-14083

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 1-7, 2014

Authors: Akrami, Seyed Mohammad | Habibi, Laleh

Article Type: Review Article

Abstract: Pediatric disorders are generally observed to have a greater genetic load than diseases occurring during adulthood. Clinical manifestations of many genetic defects including chromosomal abnormalities and mutations in specific genes appear during childhood. One of the notable mutagens in human cells is mobile DNA element. They possess the ability to move and insert themselves in new genomic locations including critical disease-causing genes. Although our cells inhibit their transport by different mechanisms, factors such as aging and environmental heavy metals have effect on increasing their activities. In this article, we try to go over the features of active human retroelements and …highlight their role in the pathology of pediatric genetic disorders. We also propose two mechanisms in which aged parental gametes and embryonic exposure to environmental stresses followed by mobile elements insertion may result in de novo pediatric diseases. Show more

Keywords: Transposable elements, pediatric genetic disorders, parental aging, heavy metals

DOI: 10.3233/PGE-14081

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 9-16, 2014

Authors: Fraga, Vanêssa Gomes | Gomes, Karina Braga

Article Type: Research Article

Abstract: The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to …provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity. Show more

Keywords: Adiponectin, adipokines, childhood obesity, polymorphisms

DOI: 10.3233/PGE-14084

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 17-28, 2014

Authors: Rush, Eric T. | Caldwell, Kathleen S. | Kreikemeier, Rose M. | Lutz, Richard E. | Esposito, Paul W.

Article Type: Research Article

Abstract: Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue typically caused by defects in either COL1A1 or COL1A2. A number of other genes causative of this disorder have been found, including PPIB, which forms one subunit of the prolyl 3-hydroxylase enzyme complex. Patients with homozygous or compound heterozygous mutations in this gene have OI with a trend toward lethal or severe phenotype. We present a Native American female with prenatal diagnosis of OI. Long bones were shortened with significant rhizomelia. At birth, fractures were present in ribs, humerii, and femurs. She had significant respiratory disease at birth, and required …oxygen throughout her life. She also had recurrent pneumonias, one of which ultimately caused her death at age 16 mo. She also had significant bilateral sensorineural hearing loss. Molecular testing showed that the patient was homozygous for a single nucleotide substitution in PPIB (c. 136-2A>G). Patients with OI caused by PPIB mutations have had variable disease, but with majority of either with perinatal lethality or progressively deforming severe disease. Patients with OI due to PPIB mutation have shown some differences in phenotype. There appears to be a trend toward rhizomelic shortening and less severe bowing of the extremities, as compared to patients with comparably severe OI caused by COL1A1 or COL1A2 mutation. Congenital hearing loss may be an inconsistent feature of this condition, or may have co-occurred in our patient for unrelated reasons. Still, patients with OI caused by PPIB mutation should have appropriate early and regular management of their hearing. Show more

Keywords: Osteogenesis imperfecta, PPIB, skeletal dysplasia, metabolic bone disease, hearing loss, collagen diseases, brittle bone disease

DOI: 10.3233/PGE-14080

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 29-34, 2014

Authors: Corradi, Massimiliano | Monti, Elena | Venturi, Giacomo | Gandini, Alberto | Mottes, Monica | Antoniazzi, Franco

Article Type: Research Article

Abstract: Recent studies have identified the molecular defect underlying autosomal dominant osteogenesis imperfecta (OI) type V. Unlike all other OI types, which are characterized by high genetic heterogeneity, OI type V appears consistently associated to a unique de novo C>T transition within the 5′ UTR of the IFITM5 gene. Although the precise frequency of OI type V is not known, this recurrent base substitution may well represent a mutational hotspot in the human genome. We show that it occurs at a CpG dinucleotide that is highly methylated in several tissues and particularly in the sperm DNA, suggesting a mutational mechanism common …to other de novo recurrent dominant mutations. Show more

Keywords: Osteogenesis imperfecta, IFITM5, DNA methylation, CpG dinucleotide deamination

DOI: 10.3233/PGE-14079

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 35-39, 2014

Authors: Jerkovich, Adria M. | Butler, Merlin G.

Article Type: Research Article

Abstract: We report a 10-year-old Caucasian male identified with copy number variation detected by microarray analysis including a maternally inherited 15q11.2 microdeletion involving 4 genes, paternally inherited 13q12.2 microdeletion with 10 genes, and a de novo 2q14.3 duplication involving four genes. He had a history of speech delay, cognitive deficits, attention deficit hyperactivity disorder and a posterior lenticonus cataract removed at 5 yr of age. The genes on chromosomes 2 and 13 are not known to be involved with cataract formation, which lends further support for a role of the 15q11.2 region and additional evidence for phenotypic expansion of the 15q11.2 …BP1-BP2 microdeletion (termed Burnside-Butler) syndrome. Show more

Keywords: Microarray analysis, motor and language delay, congenital cataracts, dysmorphic features

DOI: 10.3233/PGE-14082

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 41-44, 2014

Article Type: Other

Citation: Journal of Pediatric Genetics, vol. 3, no. 1, pp. 45-46, 2014