Prenatal diagnosis of a fetus with harlequin ichthyosis caused by novel splice-site mutation in ABCA12 gene / 中华围产医学杂志

This article reported a rare case of harlequin ichthyosis which was indicated with multiple structural abnormalities by prenatal ultrasound and diagnosed by trio-based whole-exome sequencing (Trio-WES). Prenatal diagnosis was performed because the ultrasound at 24 +4 gestational weeks revealed the fetus presenting with eclabium, flattened nose, short mandible, small auricle and abnormal posture of the toes. Copy number variation sequencing (CNV-seq) showed no chromosome aneuploidy or pathogenic copy number variants over 100 kb in the fetal or parental samples. Trio-WES showed that the fetus carried two heterozygous mutations, c.2593-1G>A and c.7444C>T in ABCA12. Sanger sequencing confirmed that c.2593-1G>A, a previously unreported variant, was paternally inherited and c.7444C>T was maternally inherited. Both parents had normal phenotype. The fetus was finally diagnosed with harlequin ichthyosis. After prenatal counseling, the parents made an informed choice to terminate the pregnancy at 28 +4 gestational weeks. The stillborn fetus showed multiple malformations The variants in this case expand the spectrum of variants in ABCA12 gene.

Supplementary value of denaturing high performance liquid chromatography for routine prenatal diagnosis of spinal muscular atrophy by multiple ligation-dependent probe amplification / 中华医学遗传学杂志

Objective@#To explore the feasibility of high performance liquid chromatography (DHPLC) combined with multiple ligation-dependent probe amplification (MLPA) for the prenatal diagnosis of spinal muscular atrophy (SMA).@*Methods@#Three families who had given birth to children with SMA type I were subjected to prenatal diagnosis. Peripheral blood samples were collected from the three couples, and 10 mL amniotic fluid was taken for each fetus through amniocentesis at 16-24 gestational week. Following DNA extraction, maternal contamination was excluded by STR analysis. Copy numbers of the SMN genes were detected by denaturing high performance liquid chromatography (DHPLC). Relative copy number of SMN1, SMN2 and reference genes was detected with a MLPA P021 assay kit.@*Results@#The three couples were all found to harbor heterozygous deletion of exon 7 of the SMN1 gene by DHPLC. MLPA analysis also suggested that the three couples were all carriers of SMA mutations. The fetus of family 1 harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus had SMA. The fetus of family 2 also harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, while the copy number of SMN2 gene was normal, suggesting that the fetus was a SMA patient too. The fetus of family 3 harbored heterozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus was a carrier.@*Conclusion@#DHPLC can effectively screen carriers of SMA mutations. Combined DHPLC and MLPA can provide accurate diagnosis for fetuses with a high risk for SMA.

Supplementary value of denaturing high performance liquid chromatography for routine prenatal diagnosis of spinal muscular atrophy by multiple ligation-dependent probe amplification / 中华医学遗传学杂志

OBJECTIVE@#To explore the feasibility of high performance liquid chromatography (DHPLC) combined with multiple ligation-dependent probe amplification (MLPA) for the prenatal diagnosis of spinal muscular atrophy (SMA).@*METHODS@#Three families who had given birth to children with SMA type I were subjected to prenatal diagnosis. Peripheral blood samples were collected from the three couples, and 10 mL amniotic fluid was taken for each fetus through amniocentesis at 16-24 gestational week. Following DNA extraction, maternal contamination was excluded by STR analysis. Copy numbers of the SMN genes were detected by denaturing high performance liquid chromatography (DHPLC). Relative copy number of SMN1, SMN2 and reference genes was detected with a MLPA P021 assay kit.@*RESULTS@#The three couples were all found to harbor heterozygous deletion of exon 7 of the SMN1 gene by DHPLC. MLPA analysis also suggested that the three couples were all carriers of SMA mutations. The fetus of family 1 harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus had SMA. The fetus of family 2 also harbored homozygous deletion of exons 7 and 8 of the SMN1 gene, while the copy number of SMN2 gene was normal, suggesting that the fetus was a SMA patient too. The fetus of family 3 harbored heterozygous deletion of exons 7 and 8 of the SMN1 gene, in addition with heterozygous deletion of exons 7 and 8 of the SMN2 gene, suggesting that the fetus was a carrier.@*CONCLUSION@#DHPLC can effectively screen carriers of SMA mutations. Combined DHPLC and MLPA can provide accurate diagnosis for fetuses with a high risk for SMA.

Role of urotensin Ⅱ gene in the genetic susceptibility to gestational diabetes mellitus in northern Chinese women / 中华妇产科杂志

Objective To investigate the relationship between the polymorphism of site rs228648 in urotensin Ⅱ gene and the genetic susceptibility to gestational diabetes mellitus in northern Chinese women. Methods Genotyping was conducted to investigate the polymorphism of site rs228648 (G—A) in urotensin Ⅱgene among 70 unrelated gestational diabetes mellitus(GDM) subjects and 70 normal controls. DNA samples isolated from leucocyte of the control and study groups were analyzed for single-nucleotide polymorphisms of the urotensin Ⅱ gene at positions rs228648 using polymerase chain reaction and restriction analysis. Results (1)The distribution of genotype frequencies of site rs228648 accorded with Hardy-Weinberg′s equation law, being colony representative.(2)The frequency of G allele of site rs228648 was 70.7% in GDM group, significantly higher than that in the control group (57.9%, P0.05). (3) Women in control group were more likely to be homozygous for the allele A of site rs228648 than women with GDM. The frequency of A/A genotype of rs228648 was negatively correlated with GDM group. By the logistic procedure, after adjustment by age and gestational weeks, the odds ratio was 0.312 , and Wald Confidence Limites were 0.108 to 0.900 (P= 0.031). Conclusion Urotensin Ⅱ gene may contribute to the genetic susceptibility to gestational diabetes mellitus in northern Chinese population. G allele of site rs228648 is related to GDM possibly, and that homozygosis A of site rs228648 is likely to be an important protecting factor for GDM.