Variant analysis for a pedigree affected with limb-girdle muscular dystrophy type 2D / 中华医学遗传学杂志

OBJECTIVE@#To analyze variant of SGCA gene in a Chinese pedigree affected with limb-girdle muscular dystrophy type 2D with whole exome sequencing (WGS).@*METHODS@#Multiplex ligation-dependent probe amplification (MLPA) was employed to detect large fragment deletion or duplication of the DMD gene. FastTarget next generation sequencing was used to detect variants of the DMD gene, and the result was verified by Sanger sequencing. After excluding the diagnosis of DMD for the proband, WGS was applied to test the proband and his parents. Suspected pathogenic variants were validated by Sanger sequencing.@*RESULTS@#No variant, deletion or duplication of the DMD gene was detected. Whole exome sequencing showed that the proband has carried compound heterozygous missense variants c.409G>A (p.Glu137Lys) and c.409G>C (p.Glu137Gln) in exon 5 of the SGCA gene, which were respectively inherited from his mother and father. Neither variant was found in DNA derived from the cord blood sample.@*CONCLUSION@#The c.409G>A (p.Glu137Lys) and c.409G>C (p.Glu137Gln) compound heterozygous missense variants probably underlie the disease in the proband. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.

Analysis of MYH3 gene variation and prenatal diagnosis for two pedigrees affected with congenital arthrogryposis / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of two pedigrees affected with congenital arthrogryposis.@*METHODS@#Whole exome sequencing (WES) was used to screen potential variations in the proband. Suspected variations were analyzed with bioinformatics software and validated by Sanger sequencing.@*RESULTS@#A heterozygous c.1123G>A (p.Glu375Lys) variation was detected in the proband and an affected fetus from pedigree 1, while a de novo heterozygous c.118 G>A (p.Val40Met) variation was detected in an affected fetus from pedigree 2.@*CONCLUSION@#The two heterozygous variations of the MYH3 gene probably underlie the disease in the pedigrees. Above results have facilitated genetic counseling and prenatal diagnosis.