RESUMEN
OBJECTIVE@#To analyze the genetic characteristics of a child with Meier-Gorlin syndrome (MGS) due to a homozygous variant of the ORC6 gene.@*METHODS@#A child who was admitted to the Children's Hospital Affiliated to Soochow University on March 25, 2019 due to growth retardation was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 8-year-and-3-month-old male, has featured short stature, small ears, bilateral cryptorchidism and patellar dysplasia. His parents were of first cousins. The child was found to harbor a homozygous c.712A>T (p.K238*) missense variant of the ORC6 gene, which may lead to premature termination of protein translation. Sanger sequencing confirmed that both of his parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP3+PP4).@*CONCLUSION@#The homozygous c.712A>T (p.K238*) variant probably underlay the MGS in this child.
Asunto(s)
Humanos , Lactante , Masculino , Biología Computacional , Microtia Congénita/genética , Enanismo/genética , Trastornos del Crecimiento/genética , Complejo de Reconocimiento del Origen/genéticaRESUMEN
<p><b>OBJECTIVE</b>To identify the genetic cause for a 11-year-old Chinese boy with Meier-Gorlin syndrome (MGS).</p><p><b>METHODS</b>Chromosomal microarray analysis (CMA) was used to detect potential variations, while whole exome sequencing (WES) was used to identify sequence variants. Sanger sequencing was used to confirm the suspected variants.</p><p><b>RESULTS</b>The boy has featured short stature, microtia, small patella, slender body build, craniofacial anomalies, and small testes with normal gonadotropin. A complete uniparental disomy of chromosome 16 was revealed by CMA. WES has identified a novel homozygous mutation c.67A>G (p.Lys23Glu) in ORC6 gene mapped to chromosome 16. As predicted by Alamut functional software, the mutation may affect the function of structural domain of the ORC6 protein.</p><p><b>CONCLUSION</b>The patient is probably the first diagnosed MGS case in China, who carried a novel homozygous mutation of the ORC6 gene and uniparental disomy of chromosome 16. The effect of this novel mutation on the growth and development needs to be further investigated.</p>
Asunto(s)
Niño , Humanos , Masculino , Secuencia de Bases , Cromosomas Humanos Par 16 , Genética , Microtia Congénita , Genética , Salud de la Familia , Padre , Trastornos del Crecimiento , Genética , Heterocigoto , Micrognatismo , Genética , Mutación , Complejo de Reconocimiento del Origen , Genética , Rótula , Anomalías Congénitas , Reacción en Cadena de la Polimerasa , Métodos , Análisis de Secuencia de ADN , Métodos , Disomía Uniparental , GenéticaRESUMEN
<p><b>OBJECTIVE</b>To explore the expression of origin recognition complex 1 (ORC1) during the DNA replication of vascular muscle cells (VSMC).</p><p><b>METHODS</b>VSMC of thoracic aorta in rats were obtained by the adherence method of tissue culture. The cell synchrony was obtained by the method of double-thymidine block, colchicine treatment and serum starvation. The expression of ORC1 mRNA at different cell cycles of VSMC was determined by RT-PCR and the protein expression of ORC1 was analyzed by Western blot.</p><p><b>RESULTS</b>Cultured VSMC were identified by light microscope and immunocytochemistry. Significant expression of ORC1 mRNA and protein in a quiescent stage of VSMC were not observed. Upon synchronization, the expression of ORC1 mRNA was significantly higher at G(1)/S phase of VSMC than that at S and G(2)/M phases. The expression of ORC1 protein followed same changes as the ORC1 mRNA expression at different stages of cell cycles.</p><p><b>CONCLUSION</b>ORC1 may be an important regulatory factor at the initiation of proliferative process of VSMC.</p>