Amyloidosis cutis dyschromica due to homozygous variants of the GPNMB gene in a Chinese pedigree / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with amyloidosis cutis dyschromica.@*METHODS@#High-throughput sequencing was carried out for the proband. Bioinformatic analysis was used to identify the pathogenic variants. The result was verified by Sanger sequencing.@*RESULTS@#A homozygous nonsense variant c.565C>T (p.Arg189X) of the GPNMB gene was identified in the proband, his elder brother and younger sister, which resulted a truncated protein with loss of function. The father of the proband was a heterozygous carrier for the variant. The genotype of his mother was unknown since she had passed away. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.565C>T variant was predicted to be likely pathogenic (PS3+ PM2+ PP1+PP3).@*CONCLUSION@#The novel homozygous GPNMB variant probably underlay the amyloidosis cutis dyschromica in this pedigree. Above finding has expanded the spectrum of GPNMB gene variants.