Analysis of LBR gene mutation in a pedigree affected with Pelger-Huёt anomaly / 中华医学遗传学杂志

OBJECTIVE@#To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly (PHA) and to explore its clinical characteristics.@*METHODS@#Genomic DNA was extracted from the pedigree and healthy controls. The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified in other family members and 100 healthy controls. Polyphen-2 and SIFT software were used to predict the effect of the mutation, and Swiss-model software was used to simulate the protein structure.@*RESULTS@#Three patients were found to carry a c.893G>A mutation in exon 8 of the LBR gene, which resulted in substitution of the 298th amino acid residue glycine by glutamic acid (p.Gly298Glu). The same mutation was not found in healthy family members and 100 healthy controls. The mutation was predicted to be damaging. Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein.@*CONCLUSION@#The c.893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.

Analysis of LBR gene mutation in a pedigree affected with Pelger-Huёt anomaly / 中华医学遗传学杂志

Objective@#To detect mutation of LBR gene in a pedigree affected with Pelger-Huёt anomaly (PHA) and to explore its clinical characteristics.@*Methods@#Genomic DNA was extracted from the pedigree and healthy controls. The 14 exons of the LBR gene were subjected to PCR amplification and Sanger sequencing. Suspected mutations were verified in other family members and 100 healthy controls. Polyphen-2 and SIFT software were used to predict the effect of the mutation, and Swiss-model software was used to simulate the protein structure.@*Results@#Three patients were found to carry a c. 893G>A mutation in exon 8 of the LBR gene, which resulted in substitution of the 298th amino acid residue glycine by glutamic acid (p.Gly298Glu). The same mutation was not found in healthy family members and 100 healthy controls. The mutation was predicted to be damaging. Bioinformatic simulation showed the mutation has altered the 3D structure of the LBR protein.@*Conclusion@#The c. 893G>A (p.Gly298Glu) mutation in the LBR gene probably underlies the PHA in this pedigree and has enriched the spectrum of LBR gene mutations.

Genetic analysis of a pedigree affected with inherited thrombocytopenia caused by a novel mutation of MYH9 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study genetic mutations and clinical features of a pedigree affected with MYH9-related disorders from Guangxi.</p><p><b>METHODS</b>Blood platelets were counted with a hemocytometer. Blood smear was carried out to detect the inclusion body in peripheral blood neutrophils. DNA and mRNA samples were extracted from blood samples from the members of the pedigree. Fragments of the MYH9 gene were amplified with PCR and directly sequenced.</p><p><b>RESULTS</b>The affected individuals presented with a triad of giant platelets, decreased platelet count and inclusion bodies in the neutrophils with variable expressivity. A heterozygous deletional mutation (c.5803delG) in exon 41 of the MYH9 gene was found in all of the 8 affected individuals, which led to a frame-shift and change of 26 amino acids at the C-end of the tail domain of nonmuscle myosin heavy chain IIA (NMMHC-IIA) (p.Ala1935Profs*12). The same mutation was not found among healthy members of the pedigree.</p><p><b>CONCLUSION</b>The c.5803delG mutation probably underlies the MYH9-related disorders in this pedigree. The mutation has altered the C-end of the tail domain of the NMMHC-IIA protein, resulting in mild clinical symptoms in the affected individuals.</p>