Journal of Pediatric Genetics - Volume 1, issue 3

Authors: Andrade, Edgard | Williams, Charles

Article Type: Other

DOI: 10.3233/PGE-2012-024

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 149-151, 2012

Authors: Lindau-Shepard, Barbara | Janik, David K. | Pass, Kenneth A.

Article Type: Research Article

Abstract: Biotinidase deficiency is an autosomal recessive syndrome caused by defects in the biotinidase gene, the product of which affects biotin metabolism. Newborn screening (NBS) for biotinidase deficiency can identify affected infants prior to onset of symptoms; biotin supplementation can resolve or prevent the clinical features. In NBS, dry blood spots (DBS) are usually tested for biotinidase enzyme activity by colorimetric analysis. By taking advantage of the multiplexing capabilities of the Luminex platform, we have developed a microsphere-based array genotyping method for the simultaneous detection of six disease causing mutations in the biotinidase gene, thereby permitting a second tier of molecular …analysis. Genomic DNA was extracted from 3.2 mm DBS. Biotinidase gene sequences, containing the mutations of interest, were amplified by multiplexed polymerase chain reaction, followed by multiplexed allele-specific primer extension using universally tagged genotyping primers. The products were then hybridized to anti-tag carrying xTAG microspheres and detected on the Luminex platform. Genotypes were verified by sequencing. Genotyping results of 22 known biotinidase deficient samples by our xTAG biotinidase assay was in concordance with the results obtained from DNA sequencing, for all 6 mutations used in our panel. These results indicate that genotyping by an xTAG microsphere-based array is accurate, flexible, and can be adapted for high-throughput. Since NBS for biotinidase deficiency is by enzymatic assay, less than optimal quality of the DBS itself can compromise enzyme activity, while the DNA from these samples mostly remains unaffected. This assay warrants evaluation as a viable complement to the biotinidase semi-quantitative colorimetric assay. Show more

Keywords: Newborn screening, biotinidase deficiency, multiplexed genotyping

DOI: 10.3233/PGE-2012-025

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 153-160, 2012

Authors: Horth, Lisa | Stacey, Michael W. | Proud, Virginia K. | Segna, Kara | Rutherford, Chelsea | Nuss, Donald | Kelly, Robert E.

Article Type: Research Article

Abstract: Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum …in children before severe symptoms present. Quantifying sex-ratio bias in probands demonstrates a highly significant male bias associated with pectus excavatum. When combined with pedigree data, sex-bias is indicative of sex-linked, sex-limited, and/or epigenetic control such as X-inactivation, reiterating a point made with pedigrees alone, which is that more than one mutation is likely responsible for this disorder. Show more

Keywords: Disease, heritable, genetic, association study

DOI: 10.3233/PGE-2012-026

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 161-173, 2012

Authors: Ben Abdallah Bouhjar, Inesse | Gmidène, Abir | Mougou-Zrelli, Soumaya | Hannachi, Hanene | Soyah, Najla | Gadour, Naoufel | Harrabi, Imed | Elghezal, Hatem | Saad, Ali

Article Type: Research Article

Abstract: Mental retardation affects 1–3% of the population. To evaluate the implication of chromosomal abnormalities in the etiology of mental retardation, 1420 patients with non-syndromic mental retardation recruited at the department of cytogenetics of Farhat Hached hospital (Sousse, Tunisia) between January 2005 and December 2009, were analyzed using standard cytogenetic techniques. Age ranged between 3 and 18 years with a median of 8 years. Chromosomal abnormalities were detected in 7.8% of patients and an increased prevalence of chromosome anomalies was observed in patients when the mental retardation is associated with a severe degree of intellectual disability, facial dysmorphic features and/or congenital …malformations or epilepsy. Show more

Keywords: Chromosomal abnormalities, congenital malformations, epilepsy, facial dysmorphism, karyotype, mental retardation

DOI: 10.3233/PGE-2012-027

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 175-180, 2012

Authors: Mateo, Elvis Cueva | Motta, Fabio José Nascimento | de Paula Queiroz, Rosane Gomes | Scrideli, Carlos Alberto | Tone, Luiz Gonzaga

Article Type: Research Article

Abstract: The matrix metalloproteinases (MMP) are endopeptidases performing proteolytic functions in the extracellular matrix and their overexpression has been suggested to be a characteristic of malignant tumors. Molecular changes such as the presence of chimeric protein Ewing’s sarcoma protein-friend leukemia virus integration 1 (EWS-FLI1) in the Ewing family of tumors (EFT) and the oncogenes C-ERBB-2, N-MYC, C-MYC in medulloblastoma (MB) promote the overexpression of MMP. In the present study, protein expression of MMP-1, -2, -3, -9 and -14 was qualitatively evaluated in 17 EFT and MB samples of children and adolescent by western blotting and optical densitometry, and the level …of gene expression of some MMPs was determined by real-time quantitative polymerase chain reaction. Five MB samples (45.4%) presented expression of the five MMPs and six samples (54.6%) presented expression of at least one of them. Four EFT samples (66.6%) presented expression of MMP-2, -9 and -14, and two samples (33.4%) presented expression of at least one of these MMPs, whereas the presence of MMP-1 and -3 was not observed. Gene analysis showed that MMP-2 had a high expression in MB, while the expression of MMP-9 and MMP-14 was higher in EFT. It has been established that the expression of the MMPs might be related to a complex pathway of gene regulation. Show more

Keywords: Matrix metalloproteinase, Ewing tumors, medulloblastomas, protein expression

DOI: 10.3233/PGE-2012-028

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 181-187, 2012

Authors: Ismail, Samira | Helmy, Nivine A. | Mahmoud, Wael M. | El-Ruby, Mona O.

Article Type: Research Article

Abstract: Interstitial deletion of the long arm of chromosome 4 is rare. Patients with interstitial deletion of the long arm of chromosome 4 differ from those with terminal deletions. Phenotypes may be variable, depending upon the specific length and location of the deleted portion. Here, we report on a boy exhibiting most of the congenital malformations encountered in terminal 4q syndrome. The conventional karyotyping and Fluorescence in-situ hybridization revealed a de novo interstitial del (4)(q31q32). The current report is a further document highlighting that deletion of segment q31 could be contributing to the expression of most of the phenotype of 4q …deletion syndrome. Using array comparative genome hybridization methodology is recommended for investigating further cases with similar segmental interstitial deletions to support and delineate findings and to define genes implicated in the pathogenesis of the disorder. Show more

Keywords: Chromosomal aberration, interstitial deletion chromosome 4(q31q32), phenotype, 4q terminal deletion syndrome

DOI: 10.3233/PGE-2012-029

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 189-194, 2012

Authors: Sinha, Rahul | Dalal, Shamsher | Raju, Uma | John, Biju M. | Negi, Vandana

Article Type: Research Article

Abstract: The chromosome 9p deletion syndrome is a rare but specific clinical event. The clinical manifestations include dysmorphic facial features (trigonocephaly, midface hypoplasia, upward slanting palpebral fissures, and a long philtrum) and psychomotor retardation. Here we report a child with chromosome 9p deletion with Duane retraction syndrome, which has never been reported in the literature before.

Keywords: 9p deletion, dysmorphism, chromosome, Duane retraction syndrome

DOI: 10.3233/PGE-2012-030

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 195-197, 2012

Authors: Bowers, Megan | Gold-von Simson, Gabrielle

Article Type: Research Article

Abstract: An adolescent female with Moebius syndrome developed paroxysmal hypertension, orthostatic hypotension and autonomic symptoms. Common causes of dysautonomia were excluded by the work-up, which supported a diagnosis of baroreflex failure. Neurological testing suggested dysfunction of the tenth cranial nerve as the etiology. This report suggests that baroreflex dysfunction should be considered in Moebius syndrome patients displaying autonomic symptoms.

Keywords: Baroreflex failure, Moebius syndrome

DOI: 10.3233/PGE-2012-031

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 199-203, 2012

Authors: Balkan, Mahmut | Fidanboy, Mehmet | Özmen, Cihan | Özbek, M. Nuri | Otçu, Selçuk | Kapı, Emin | Budak, Turgay

Article Type: Research Article

Abstract: Trisomy 8 is a relatively rare chromosomal abnormality. The majority of cases present with the mosaic form. Regular trisomy 8 is usually lethal and frequently results in miscarriage, while those with “trisomy 8 mosaicism” are more likely to survive. We report clinical observations and cytogenetic studies of a 13-year-old male with regular trisomy 8 and compared with those of other known cases of trisomy 8. The most discriminating findings for this condition are skeletal anomalies, restricted articular function, and speech problems. Our results are in agreement with those of previous studies for trisomy 8.

Keywords: Trisomy 8, skeletal anomalies, restricted articular function, chromosome

DOI: 10.3233/PGE-2012-032

Citation: Journal of Pediatric Genetics, vol. 1, no. 3, pp. 205-208, 2012