Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs.

Phytate-mediated phosphorylation of starch by dry heating with rice bran extract.

Rice and corn starches were subjected to dry heating with rice bran extract or sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) for starch phosphorylation. Phytate in rice bran extract or STMP/STPP increased the concentration of phosphorus in rice and maize starches. The highest concentrations of phosphorus were induced in rice starch with rice bran extract and in corn starch with STMP/STPP. 31P NMR analysis indicated that the rice bran extract and STMP/STPP produced monostarch monophosphate under the same reaction conditions. Rice and corn starches phosphorylated with rice bran extract or STMP/STPP demonstrated great peak viscosity and low pasting temperatures. Although starch phosphorylated with either rice bran extract or STMP/STPP showed higher paste clarity, solubility, and swelling power than native starch, these parameters were optimal in rice starch phosphorylated with rice bran extract. Therefore, dry heating with rice bran extract induced phytate-mediated phosphorylation with the typical physicochemical properties of starch phosphates.