Comprehensive functional characterization of a novel ANO6 variant in a new patient with Scott syndrome.

BACKGROUND: Scott syndrome is a mild platelet-type bleeding disorder, first described in 1979, with only 3 unrelated families identified through defective phosphatidylserine (PS) exposure and confirmed by sequencing. The syndrome is distinguished by impaired surface exposure of procoagulant PS on platelets after stimulation. To date, platelet function and thrombin generation in this condition have not been extensively characterized. OBJECTIVES: Genetic and functional studies were undertaken in a consanguineous family with a history of excessive bleeding of unknown cause. METHODS: A targeted gene panel of known bleeding and platelet genes was used to identify possible genetic variants. Platelet phenotyping, flow adhesion, flow cytometry, whole blood and platelet-rich plasma thrombin generation, and specialized extracellular vesicle measurements were performed. RESULTS: We detected a novel homozygous frameshift variant, c.1943del (p.Arg648Hisfs∗23), in ANO6 encoding Anoctamin 6, in a patient with a bleeding history but interestingly with normal ANO6 expression. Phenotyping of the patient's platelets confirmed the absence of PS expression and procoagulant activity but also revealed other defects including reduced platelet δ granules, reduced ristocetin-mediated aggregation and secretion, and reduced P-selectin expression after stimulation. PS was absent on spread platelets, and thrombi formed over collagen at 1500/s. Reduced thrombin generation was observed in platelet-rich plasma and confirmed in whole blood using a new thrombin generation assay. CONCLUSION: We present a comprehensive report of a patient with Scott syndrome with a novel frameshift variant in AN06, which is associated with no platelet PS exposure and markedly reduced thrombin generation in whole blood, explaining the significant bleeding phenotype observed.

Socioeconomic Status and Parental Perceived Social Support in Relation to Health-Related Quality of Life in Youth with Spina Bifida.

Spina bifida (SB) is a congenital birth defect causing a wide variance of physical and intellectual disabilities. The first objective of this study was to examine SES and parental perceived support as predictors of HRQoL among youth with SB. It was hypothesized that lower SES would predict lower youth HRQoL, and higher parental perceived support would predict higher youth HRQOL. The second objective of this study was to examine parental perceived support as a moderator of the association between SES and youth HRQoL. Parental perceived support was hypothesized to serve as a buffer of the negative impact that low SES has on HRQoL. Results indicated significant effects of SES on school, physical, and total HRQoL subscales when covariates were not included. In addition, parental perceptions of social support from family members were significantly associated with Emotional HRQoL in youth with SB. There was a significant interaction between SES and parental perceived support from friends predicting youth Social HRQoL. However, post-hoc simple slope analyses were not significant. This study works to expand the understanding of the roles of SES and parental perceived social support on the HRQoL in children with SB, a population susceptible to poor quality of life due to the physical and cognitive challenges commonly associated with this condition.