BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somati...BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somatic mosaicisms are usually recognized in the parents only after a typically affected son is diagnosed with KBG syndrome.We describe for the first time the mosaicism of a novel variant in a child with a mild KBG phenotype.CASE SUMMARY Our patient presented at 24 mo of age with short stature,hand abnormalities,facial dysmorphism and mild developmental delay.Pituitary hypoplasia and central hypothyroidism were also detected.By next generation sequencing(NGS)analysis we found a novel deletion in the ANKRD11 gene(c.4880_4893del.),that can be classified as likely pathogenic for the syndrome,with the percentage of mutated allele of 36%.We considered this finding as causative of the mild and non-specific phenotype for KBG syndrome in our patient,as previously reported in adults.A heterozygous variant in HESX1 gene,classified as variant of uncertain significance,but suspected of causing pituitary hypoplasia and hormonal deficiency,was also found.The patient started levothyroxine and growth hormone treatment.CONCLUSION The increased use of NGS analysis may expand the phenotypic spectrum of KBG syndrome because it allows genetic diagnosis of somatic mosaicisms also in children.展开更多
In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of β-catenin protein, the expression of β-catenin/TCF signaling pathway target gene cyclinD1 mRNA, and cell cycle of Jurk...In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of β-catenin protein, the expression of β-catenin/TCF signaling pathway target gene cyclinD1 mRNA, and cell cycle of Jurkat cell line （Human T-acute lymphoblastic leukemia）. Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of β-catenin, and at 5 mmol/L of aspirin, the nuclear localization of β-catenin was undetectable. QRT-PCR showed that the target gene cyclinDl mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1 cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through β-catenin-independent mechanisms. The effects of aspirin include down-regulation of β-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line.展开更多
文摘BACKGROUND KBG syndrome is likely underdiagnosed because of mild and non-specific features in some affected patients especially before the upper permanent central incisors eruption at about the age of 7-8 years.Somatic mosaicisms are usually recognized in the parents only after a typically affected son is diagnosed with KBG syndrome.We describe for the first time the mosaicism of a novel variant in a child with a mild KBG phenotype.CASE SUMMARY Our patient presented at 24 mo of age with short stature,hand abnormalities,facial dysmorphism and mild developmental delay.Pituitary hypoplasia and central hypothyroidism were also detected.By next generation sequencing(NGS)analysis we found a novel deletion in the ANKRD11 gene(c.4880_4893del.),that can be classified as likely pathogenic for the syndrome,with the percentage of mutated allele of 36%.We considered this finding as causative of the mild and non-specific phenotype for KBG syndrome in our patient,as previously reported in adults.A heterozygous variant in HESX1 gene,classified as variant of uncertain significance,but suspected of causing pituitary hypoplasia and hormonal deficiency,was also found.The patient started levothyroxine and growth hormone treatment.CONCLUSION The increased use of NGS analysis may expand the phenotypic spectrum of KBG syndrome because it allows genetic diagnosis of somatic mosaicisms also in children.
文摘In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of β-catenin protein, the expression of β-catenin/TCF signaling pathway target gene cyclinD1 mRNA, and cell cycle of Jurkat cell line （Human T-acute lymphoblastic leukemia）. Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of β-catenin, and at 5 mmol/L of aspirin, the nuclear localization of β-catenin was undetectable. QRT-PCR showed that the target gene cyclinDl mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1 cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through β-catenin-independent mechanisms. The effects of aspirin include down-regulation of β-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line.
