Analysis of ALPL gene variant in a patient with infantile hypophosphatasia / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a girl featuring bone and tooth mineralization disorder, premature deciduous teeth, rickets and short stature.@*METHODS@#Genomic DNA was extracted and subjected to high-throughput whole exome sequencing. Suspected variants were confirmed by Sanger sequencing. Impact of potential variants was analyzed with bioinformatic software.@*RESULTS@#The child was found to carry compound heterozygous missense variants of the ALPL gene, including c.1130C>T (p.A377V), a known pathogenic mutation inherited from her father, and c.1300G>A (p.V434M) inherited from her mother, which was unreported previously and predicted to be likely pathogenic based on standards and guidelines from the American College of Medical Genetics and Genomics (PM2+PM5+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants of c.1130C>T (p.Ala377Val) and c.1300G>A (p.Val434Met) of the ALPL gene probably underlay the disease in this child. Above finding has enriched the spectrum of ALPL gene variants.

Mutation analysis of a pedigree affected with brachydactyly type E2 and obesity / 中华医学遗传学杂志

OBJECTIVE@#To identify pathogenic mutation in a pedigree affected with brachydactyly and obesity.@*METHODS@#Peripheral blood sample was collected for extraction of genomic DNA. Exons capture combined with next generation sequencing (NGS) was carried out to identify potential mutation. Sanger sequencing was used to verify the results.@*RESULTS@#NGS has identified a novel heterozygous missense mutation (c.125A>C, p.Gln42Pro) in the exon 1 of PTHLH gene. The result was verified by Sanger sequencing. The mutations was derived from his mother. His uncle and sister have also carried the same heterozygous mutation.@*CONCLUSION@#A novel mutation of the PTHLH gene has been identified in a pedigree affected with brachydactyly type E2 and obesity.

Analysis of clinical and genetic results in one case of very long chain acyl-CoA dehydrogenase deficiency / 中华内分泌代谢杂志

Clinical characteristics were analyzed in a child with very long chain acyl-CoA dehydrogenase deficiency( VLCADD) . The gene analysis was performed in 20 exon all coding regions and 10 bp shear zone in the very long chain acyl-CoA dehydrogenase( VLCAD) gene of the case and his family members by direct sequencing of PCR-DNA from peripheral blood. The results showed that the patient presented with acute onset, clinical manifestations of repeated vomiting, poor spirit, abnormal liver function, increased myocardial enzyme kinase. At the age of one year old, this child was diagnosed with Reye's syndrome for liver injury. Genetic testing results revealed that E14 c. 1349G>A, p. R450H heterozygous mutation in VLCAD gene was found in this case, his mother, and his younger sister, and E15 c. 1532G>A, p. R511Q heterozygous mutation was found in this case and his father. The pathogenic genes of the case are from his mother and the younger sister is a carrier.