Background A child with autism and mild microcephaly was found to have a de novo 3.3 Mb microdele... more Background A child with autism and mild microcephaly was found to have a de novo 3.3 Mb microdeletion on chromosome 1p34.2p34.3. The hypothesis is tested that this microdeletion contains one or more genes that underlie the autism phenotype in this child and in other children with autism spectrum disorders. Methods To search for submicroscopic chromosomal rearrangements in the child, array comparative genomic hybridisation (aCGH) was performed using a 19 K whole genome human bacterial artificial chromosome (BAC) array and the Illumina 610-Quad BeadChip microarray. Ingenuity pathway analysis (IPA) was used to construct functional biological networks to identify candidate autism genes. To identify putative functional variants in candidate genes, mutation screening was performed using polymerase chain reaction (PCR) based Sanger sequencing in 512 unrelated autism patients and 462 control subjects. Results A de novo 3.3 Mb deletion containing w43 genes in chromosome 1p34.2p34.3 was identified and subsequently confirmed using fluorescence in situ hybridization (FISH). Literature review and bioinformatics analyses identified Regulating Synaptic Membrane Exocytosis 3 (RIMS3) as the most promising autism candidate gene. Mutation screening of this gene in autism patients identified five inherited coding variants, including one (p.E177A) that segregated with the autism phenotype in a sibship, was predicted to be deleterious, and was absent in 1161 controls. Conclusions This case report and mutation screening data suggest that RIMS3 is an autism causative or contributory gene. Functional studies of RIMS3 variants such as p.E177A should provide additional insight into the role of synaptic proteins in the pathophysiology of autism.
This review updates and complements the review of energy balance and body composition in the Proc... more This review updates and complements the review of energy balance and body composition in the Proceedings of the 2003 IOC Consensus Conference on Sports Nutrition. It argues that the concept of energy availability is more useful than the concept of energy balance for managing the diets of athletes. It then summarizes recent reports of the existence, aetiologies, and clinical consequences of low energy availability in athletes. This is followed by a review of recent research on the failure of appetite to increase ad libitum energy intake in compensation for exercise energy expenditure. The review closes by summarizing the implications of this research for managing the diets of athletes.
Background A child with autism and mild microcephaly was found to have a de novo 3.3 Mb microdele... more Background A child with autism and mild microcephaly was found to have a de novo 3.3 Mb microdeletion on chromosome 1p34.2p34.3. The hypothesis is tested that this microdeletion contains one or more genes that underlie the autism phenotype in this child and in other children with autism spectrum disorders. Methods To search for submicroscopic chromosomal rearrangements in the child, array comparative genomic hybridisation (aCGH) was performed using a 19 K whole genome human bacterial artificial chromosome (BAC) array and the Illumina 610-Quad BeadChip microarray. Ingenuity pathway analysis (IPA) was used to construct functional biological networks to identify candidate autism genes. To identify putative functional variants in candidate genes, mutation screening was performed using polymerase chain reaction (PCR) based Sanger sequencing in 512 unrelated autism patients and 462 control subjects. Results A de novo 3.3 Mb deletion containing w43 genes in chromosome 1p34.2p34.3 was identified and subsequently confirmed using fluorescence in situ hybridization (FISH). Literature review and bioinformatics analyses identified Regulating Synaptic Membrane Exocytosis 3 (RIMS3) as the most promising autism candidate gene. Mutation screening of this gene in autism patients identified five inherited coding variants, including one (p.E177A) that segregated with the autism phenotype in a sibship, was predicted to be deleterious, and was absent in 1161 controls. Conclusions This case report and mutation screening data suggest that RIMS3 is an autism causative or contributory gene. Functional studies of RIMS3 variants such as p.E177A should provide additional insight into the role of synaptic proteins in the pathophysiology of autism.
This review updates and complements the review of energy balance and body composition in the Proc... more This review updates and complements the review of energy balance and body composition in the Proceedings of the 2003 IOC Consensus Conference on Sports Nutrition. It argues that the concept of energy availability is more useful than the concept of energy balance for managing the diets of athletes. It then summarizes recent reports of the existence, aetiologies, and clinical consequences of low energy availability in athletes. This is followed by a review of recent research on the failure of appetite to increase ad libitum energy intake in compensation for exercise energy expenditure. The review closes by summarizing the implications of this research for managing the diets of athletes.
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