The main goal of this project is to investigate around 30 patients with osteopetrosis and renal tubular acidosis (OPRTA) patients some of them were also found to be autistic. A region of 180 Kb where carbonic anhydrase II, the deficient protein in osteopetrosis and renal tubular acidosis is centered, will be studied for (1) polymorphic markers, (2) carbonic anhydrase II gene mutations; (3) inversion within the region or (4) possible micro-deletion in the region and 5) the microarray gene expression studies will be performed to identify relevant pathways. It is anticipated that a gene or genes linked to autism will be thus identified and should contribute to the research on autism-associated gene markers.

Nadia Sakati, MD, Pinar Ozand, MD, PhD, Brian Meyer, Phd, Ali Al-Odaib, PhD, Dilek Colak, PhD, Michael Nester, PhD

1) The blood samples were collected from 31 subjects and performed mutation analysis on the patients.
2) Previously we have performed microarray based gene expression studies on the collected blood samples from the 31 subjects using Affymetrix GeneChip System. We finalized this part of the project but the data analysis was ongoing. During the current progress period, high level gene expression analysis was finalized by Dr. Dilek Colak. Currently, Dr. Colak is performing pathway analysis on the data. In this report we present the results of the high level gene expression analysis as well as preliminary data from the pathway analysis.
3) We performed copy number analysis and linkage analysis on one family with three affected individuals with OPRTA and autism, and reported showed our aCGH results. This was the only family we had with three affected individuals with autism.
4) After consulting with Dr. Sakati, we understand that there are more OPRTA families having three or more affected individuals with either autism or mental retardation. Including these families with autism and mental retardation to the study is critical to complete our linkage and copy number studies. This will help us to improve the study as well as increase the power of our linkage and copy number studies. Therefore, we need an extension of one year to finalize our linkage and copy number based studies.

King Faisal Specialist Hospital & Research Center

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