Journal of Pediatric Genetics - Volume 1, issue 4

Authors: Ludwig, Michael | Reutter, Heiko

Article Type: Review Article

Abstract: Development of the genitourinary tract requires spatiotemporal expression of a myriad of genes involved in various cascades and signaling events. To date, researchers have put great efforts into defining the etiology of these malformations. However, many aspects remain unsolved. This paper reviews the most recent progress in identifying causally related genes and novel loci assumed to harbor genes involved in the formation of urogenital malformations. These investigations have been considerately accelerated by the implementation of molecular karyotyping using array techniques and next generation sequencing strategies.

Keywords: Array analysis, disease loci, genitourinary malformations, next generation sequencing

DOI: 10.3233/PGE-12033

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 209-216, 2012

Authors: Mohammad Akrami, Seyed

Article Type: Review Article

Abstract: Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage.

Keywords: Consanguineous marriage, genetic counseling, autosomal recessive disorders

DOI: 10.3233/PGE-12034

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 217-220, 2012

Authors: Deepak, Rani R. | Ashavaid, Tester F.

Article Type: Research Article

Abstract: Cystic fibrosis (CF) has been observed to be far more common in India, than was previously thought. Variability in CF clinical symptoms among individuals, results in diagnostic errors. Also, CF diagnostic facilities are not available at all diagnostic centers across India. Sweat test (gold standard for CF diagnosis) has some limitations. Mutation analysis, therefore, would be useful in detecting the mutant CF alleles in Indian patients. This study, aimed at identifying common CF transmembrane conductance regulator (CFTR) mutations, to develop a molecular diagnostic test in Indian patients, and establish genotype-phenotype correlation. Mutation identification was performed by single stranded conformation polymorphism …(SSCP) screening, followed by DNA sequencing of regions with an abnormal SSCP pattern. ∆F508 accounts for about 53% of CF alleles. A substantial proportion of these patients have rare and/or novel mutations. Eight novel and 12 known polymorphisms were also identified. Considering the high percentage of rare/novel mutations, along with ethnic history of Indian population, we can speculate that the remaining uncharacterized mutations might also not be prevalent mutations. The total number of CF disease-causing mutations in Indian patients is very large. Thus, DNA-based population screening will be complicated, and an indirect genetic diagnosis (screening entire gene) would be necessary to characterize all mutations. Show more

Keywords: Cystic fibrosis, sweat chloride, single stranded conformation polymorphism, PCR, India, molecular diagnosis, genotype, phenotype, mutations

DOI: 10.3233/PGE-12035

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 221-227, 2012

Authors: De Luca, Maria | Chandler-Laney, Paula C. | Wiener, Howard | Fernandez, Jose R.

Article Type: Research Article

Abstract: Laminins are glycoproteins found in basement membranes where they play a vital role in tissue architecture and cell behavior. Previously, we reported the association of two polymorphisms (rs659822 and rs944895) in the laminin alpha5 (LAMA5 ) gene with anthropometric traits, fasting lipid profile, and glucose levels in pre-menopausal women and elderly subjects. Furthermore, studies in mice showed that Lama5 is involved in organogenesis and placental function during pregnancy. The objective of this study was to investigate whether rs659822 and/or rs944895 are associated with inter-individual variability in birth weight as well as anthropometric traits and metabolic phenotypes in children. Two …hundred and eighty nine healthy children aged 7–12 yr of European, Hispanic, and African-American ancestry were studied. Co-dominant models adjusted for genetic admixture, age, gender, and stages of puberty were used to test for the association of the polymorphisms with each trait. Our analysis showed significant associations of rs659822 with fasting plasma glucose levels (P = 0.0004) and of rs944895 with fasting serum triglycerides (P = 0.004) after Bonferroni correction for multiple testing. Our results corroborate our previous findings that genetic variants in LAMA5 contribute to variation in metabolic phenotypes and provide evidence that this may occur early in life. Show more

Keywords: Laminins, lipid profile, glycemia, birth weight, genetic variants

DOI: 10.3233/PGE-12036

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 229-234, 2012

Authors: Crespo, Frank | Pinar, Halit | Kostadinov, Stefan

Article Type: Research Article

Abstract: We report two cases of limb-body wall complex (LBWC), also known as body stalk anomaly, a rare form of body wall defect incompatible with life. The first case was identified during a level II ultrasound examination performed at 7 wk gestational age. The delivery was by breech extraction at 39 wk and 4 days. The second case was delivered by spontaneous vaginal delivery at 35 wk and 5 days. Karyotype analysis was normal in both fetuses. The phenotype of LBWC is variable, but commonly identified features include: exencephaly, limb defects, and either facial clefts or thoraco-abdominoschisis. The exact etiology remains …uncertain, as the disorder has been regarded as sporadic with low recurrence. Vascular disruption during early embryogenesis, early amnion rupture, abnormal splitting of the embryo, and failure of amnion fusion have been implicated in the pathogenesis of LBWC. A role for possible gene mutation and maternal use of alcohol, tobacco, or illicit drugs has also been suggested. Detailed ultrasonography along with biochemical screening may allow for early detection. Show more

Keywords: Abdominal wall/abnormalities, fetus/pathology, limb defects, pregnancy, thoracic wall/abnormalities, limb-body wall complex

DOI: 10.3233/PGE-12037

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 235-238, 2012

Authors: Balkan, Mahmut | Fidanboy, Mehmet | Özbek, M. Nuri | Alp, M. Nail | Budak, Turgay

Article Type: Research Article

Abstract: We report a case with different chromosome Y abnormalities. Case was an 11-year-old boy, who was diagnosed with short stature, referred to laboratory of human medical genetics laboratory for genetic evaluation. Chromosomal analysis of the case was carried out on peripheral blood lymphocyte culture. Classic cytogenetic analysis (G and C banding) was confirmed by using fluorescence in situ hybridization analysis (FISH) technique. Cytogenetic and FISH analysis showed a mosaic 46,X,i(Yq)/45,X/47,X,i(Yq)x2/47,XYY karyotype. Case, which was found interesting due to its rarity, is discussed with its clinical features and cytogenetic results, in the light of relevant source information. This case underlines the …importance of karyotyping patients with unexplained short stature. This clinical report also will be helpful in defining the phenotypic range associated with these karyotypes. Show more

Keywords: Y chromosome, short stature, mosaicism, FISH

DOI: 10.3233/PGE-12038

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 239-242, 2012

Authors: Balkan, Mahmut | Fidanboy, Mehmet | İsi, Hilmi | Akbaş, Halit | Kalkanli, Sevgi | Alp, M. Nail | Budak, Turgay

Article Type: Research Article

Abstract: We report a case of complete tetraploidy in amniotic fluid culture obtained at 17 wk of pregnancy. Amniocentesis was performed in this pregnancy because of a high-risk maternal serum screening result and abnormal ultrasound findings. Amniotic fluid was cultured in two flasks. Growth was very slow in one culture with no growth in the other. Harvest was possible after 3 wk, which revealed tetraploidy in all studied plates. Subsequent cordocentesis was performed to confirm the diagnoses of amniocentesis. Chromosomal analysis of the cordocentesis revealed a normal karyotype with 46,XY. A healthy male infant was born at term. This case illustrates …that abnormal karyotypes in poor growth cultures could be misleading and should be confirmed by another technique, such as cordocentesis. Show more

Keywords: Amniocentesis, cordocentesis, prenatal diagnosis, tetraploidy

DOI: 10.3233/PGE-12039

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 243-246, 2012

Authors: Balasubramanian, Meena | Smith, Kath | Williams, Steve | Griffiths, Paul D. | Parker, Michael J. | Mordekar, Santosh R.

Article Type: Research Article

Abstract: Sub-telomeric deletions of the short arm of chromosome 6 are a well-described clinical entity characterized by developmental impairment, hypotonia, eye abnormalities and defects in the heart and kidneys. Chromosome 5p terminal duplication is a rarer entity, associated with developmental impairment and facial dysmorphism. We report a 3-year-old patient with a chromosome 6p25.1pter deletion and chromosome 5p15.1pter duplication who had global developmental impairment and unusual cerebral white matter changes, with hypoplastic corpus callosum and cerebellar vermis on magnetic resonance imaging -brain scan. We discuss the differential diagnosis to consider in patients with this appearance on magnetic resonance imaging -brain scan and …reiterate the need for chromosome analysis in patients with this pattern of developmental anomaly. Tigroid pattern of cerebral white matter involvement has not been reported in chromosomal deletion/duplication syndromes. With the increasing use of molecular karyotyping for patients with multiple congenital anomalies and developmental delay, it is important to consider the exact size and nature of chromosomal deletion/duplication, in order to provide families with prognostic information and recurrence risk. This in turn, will help provide valuable information regarding the natural history of rare chromosomal imbalances. Show more

Keywords: Karyotype, array CGH, tigroid appearance, developmental delay, recurrence risk

DOI: 10.3233/PGE-12040

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 247-252, 2012

Article Type: Other

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 253-256, 2012

Article Type: Other

Citation: Journal of Pediatric Genetics, vol. 1, no. 4, pp. 257-258, 2012