ABSTRACT
Autism is a childhood-onset neurodevelopmental disorder with complex genetic mechanism underlying its etiology. Recent studies revealed that a few single de novo copy number variants of genomic DNA (copy number variants [CNVs]) are pathogenic and causal in some sporadic cases, adding support to the hypothesis that some sporadic autism might be caused by single rare mutation with large clinical effect. In this study, we report the detection of two novel private CNVs simultaneously in a male patient with autism. These two CNVs include a microduplication of ~4.5 Mb at chromosome 4q12-13.1 that was transmitted from his mother and a microdeletion of ~1.8 Mb at 5q32 that was transmitted from his father. Several genes such as LPHN3, POU4F3, SH3RF2, and TCERG1 mapped to these two regions have psychiatric implications. However, the parents had only mild degree of attention deficit symptoms but did not demonstrate any obvious autistic symptoms or psychopathology. Our findings indicate that each of these two CNVs alone may not be pathogenic enough to cause clinical symptoms in their respective carriers, and hence they can be transmitted within each individual family. However, concomitant presence of these two CNVs might result in the clinical phenotypes of the affected patient reported here. Thus, our report of this family may represent an example to show that two hits of CNV and the presence of compound heterozygosity might be important mechanisms underlying the pathogenesis of autism.
Subject(s)
Autistic Disorder/genetics , DNA Copy Number Variations/genetics , Genetic Predisposition to Disease , Heterozygote , Inheritance Patterns/genetics , Models, Genetic , Adolescent , Adult , Base Pairing/genetics , Child , Child, Preschool , Chromosome Deletion , Chromosome Duplication/genetics , Chromosomes, Human, Pair 4/genetics , Chromosomes, Human, Pair 5/genetics , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , Reproducibility of Results , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND: Intrathecal midazolam acts synergically with other anesthetics to relieve surgical pain, and the drug combination may decrease complications attributable to each component drug. This prospective study was to determine the spinal effects of low-dose of bupivacaine (5 mg) combined with intrathecal midazolam (2 mg) in diabetes mellitus (DM) patients undergoing foot debridement. METHODS: Sixty diabetic patients were admitted for foot debridement under spinal anesthesia were equally divided into two groups. Group 1 (M) received 7.5 mg of hyperbaric bupivacaine; group 2 (M+M) received 5 mg of hyperbaric bupivacaine combined with 2 mg of midazolam intrathecally. The intensity of motor block was assessed with modified Bromage scale 20 minutes after injection, and at 0, 30, 60, 90 and 120 min after arriving at the post anesthesia care unit (PACU). Pain score was assessed with a 10 cm visual analog scale (VAS, 0 = no pain and 10 = intolerable pain) at 0, 1, 2, 6 h and 24 h postoperatively. RESULTS: Anesthesia was smooth in all patients except one in group M, whose analgesia was inadequate and general anesthesia was given to complete the surgery. The number of patients who sustained moderate to severe pain (VAS > 5) was significantly less in the M+M group than in M group as accessed 6 and 24 h postoperatively. The requirement of additional analgesic as reinforcement was significantly less in the M+M group than in the M group within the space of 24 h postoperatively. Recovery of motor function was significantly faster in the M+M group. CONCLUSIONS: The combination of intrathecal midazolam and bupivacaine was a safe and effective anesthetic technique, and it also provided early recovery of motor function and reduced the requirement of analgesics postoperatively.
