Friday, May 18, 2012: 11:00 AM
Grand Ballroom East (Sheraton Centre Toronto)
10:15 AM
C. M. Ribeiro1, V. N. Takahashi
2, D. P. Moreira
1, M. G. Rodrigues
1, K. Griesi-Oliveira
1, C. Rosenberg
1, D. R. Bertola
1, E. Vasdasz
3 and M. R. Passos-Bueno
1, (1)Department of Genetics and Evolutionary Biology, University Sao Paulo, Biosciences Institute, Sao Paulo, Brazil, (2)Human Genome Center, University of Sao Paulo, Sao Paulo, Brazil, (3)Department of Psychiatry Faculty of Medicine, Institute of Psychiatry, Hospital of the Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil
Background: We report a case of a teenager (16 years, RBR) boy with the clinical diagnosis of Asperger syndrome. RBR presents anxiety, hyperactivity, severe impairment of social interaction, restricted and repetitive patterns of behavior, interests and activities, marked deficiency in the use of nonverbal behaviors, failure to recognize and to use the conventional rules of conversation, failure to recognize the use of irony, slang, sarcasm and metaphors. No significant dysmorphic features were noted and anthropometric measurements were within normal range. During the anamnesis the family reported that RBR has one first (SMRF) and two second degree (VRPA and MRPA) males paternal cousins with similar phenotype. These affected individuals were later evaluated and we verified that SMRF had also been previously diagnosed with Asperger syndrome, with a phenotype very similar to RBR. On the other hand, MRPA, previously diagnosed as autistic, differs from RBR by the manifestation of aggressive behavior, stereotyped and repetitive motor mannerisms, and lack of verbal communication. VRPA, has yet to be evaluated by us but his parents reported that his behavior is different from other boys of his own age. VRPA presents difficulties in social interaction, restricted pattern of interests, elaborate speech and remarkable ability to perform mathematical calculations.
Objectives: To investigate the causative genetic mechanisms of the phenotypes of the individuals in this family.
Methods: Patients were previously excluded for Fragile X syndrome. To screen for causative chromosome imbalances, we did MLPA (SALSA MLPA KIT P343 AUTISM-B1-1 and SALSA MLPA KIT P070 HUMAN Telomere-5-HOLLAND MLPA MRC), customized CGH-microarray (Agilent Techonologies _8x60K format) and SNP-array (GeneChip Human Mapping Affymetrix 500K Array Set) techniques.
Results: The custom array-CGH revealed a deletion of the gene IMMP2L (IMP2 inner mitochondrial membrane peptidase-like) in subject RBR. This deletion was confirmed by the use of the SNP-array technique. In addition, no other mutation was observed. This gene encodes a protein involved in processing the signal peptide sequences used to direct proteins to the mitochondria. The encoded protein resides in the mitochondria and is necessary for the catalytic activity of the mitochondrial inner membrane peptidase (IMP) complex. Genetic variation in IMMP2L has previously been associated with autism. The mutation seen in the individual RBR was inherited from his father and is also present in his paternal cousins SMRF and MRPA, but not in VPRA.
Conclusions: The results obtained so far provide evidence that the IMMP2L deletion may be partially responsible for the subject’s phenotypes.
