Sleep related breathing disorders in the spina bifida population ages 1-20 years: A retrospective study in Arkansas.

PURPOSE: Sleep related breathing disorders (SRBD) are seen at disproportionately higher rates in children with spina bifida compared with their same aged peers. SRBD such as obstructive sleep apnea (OSA) or central apnea are associated with developmental and cognitive consequences, and sudden death. METHODS: Participants aged 1 to 20 years with a diagnosis of spina bifida were recruited from a pediatric academic hospital spinal cord specialty clinic to evaluate the prevalence and impact of sleep disorders in the spina bifida population; 76 polysomnogram (PSG) reports spanning a 3-year period were reviewed in this retrospective cohort study. RESULTS: Of the PSGs reviewed, 37 (49%) indicated the presence of SRBD, and 28 (76%) of those children required an escalation of management (surgical intervention or additional respiratory support). These results are consistent with previous studies and further emphasize the clinical impact of SRBD on children with spina bifida by describing the interventions that followed an abnormal PSG. CONCLUSION: The high prevalence of SRBD in the spina bifida population supports the need for additional research to develop sleep questionnaires specific to spina bifida that can predict abnormal PSG clinically and to determine the standard of care following an abnormal PSG, chiefly in OSA and central apnea.

Dominant effects of the histone mutant H3-L61R on Spt16-gene interactions in budding yeast.

Recent studies have unveiled an association between an L61R substitution within the human histone H3.3 protein and the presentation of neurodevelopmental disorders in two patients. In both cases, the mutation responsible for this substitution is encoded by one allele of the H3F3A gene and, if this mutation is indeed responsible for the disease phenotypes, it must act in a dominant fashion since the genomes of these patients also harbour three other alleles encoding wild-type histone H3.3. In our previous work in yeast, we have shown that most amino acid substitutions at H3-L61 cause an accumulation of the Spt16 component of the yFACT histone chaperone complex at the 3' end of transcribed genes, a defect we have attributed to impaired yFACT dissociation from chromatin following transcription. In those studies, however, the H3-L61R mutant had not been tested since it does not sustain viability when expressed as the sole source of histone H3 in cells. In the present work, we show that H3-L61R impairs proper Spt16 dissociation from genes when co-expressed with wild-type histone H3 in haploid cells as well as in diploid cells that express the mutant protein from one of four histone H3-encoding alleles. These results, combined with other studies linking loss of function mutations in human Spt16 and neurodevelopmental disorders, provide a possible molecular mechanism underlying the neurodevelopmental disorders seen in patients expressing the histone H3.3 L61R mutant.