FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome

Abstract

We describe a patient with autism and brachymetaphalangy, meeting criteria for 2q37 deletion syndrome (also called Albright Hereditary Osteodystrophy-like syndrome or Brachydactyly-Mental Retardation syndrome, OMIM 600430). Our molecular cytogenetic studies, including array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH), define the extent of the de novo deletion to a 3.5 Mb region on 2q37.3. Although a number of reports of patients with 2q37 deletion syndrome have been published, it remains unclear if gene expression and/or translation are altered by the deletion, thus contributing to the observed phenotypes. To address this question, we selected several candidate genes for the neuropsychiatric and skeletal anomalies found in this patient (autism and brachymetaphalangy). The deleted region in 2q37.3 includes the FERM, RhoGEF and pleckstrin domain protein 2 (FARP2), glypican 1 (GPC1), vigilin (HDLBP), kinesin family member 1A (KIF1A) and proline-alanine-rich STE20-related kinase (PASK), all of which are involved in skeletal or neural differentiation processes. Expression analyses of these genes were performed using RNA from lymphoblastoid cell lines of the patient and his family members. Here we demonstrate that three of these genes, FARP2, HDLBP, and PASK, are considerably downregulated in the patient's cell line. We hypothesize that haploinsufficiency of these genes may have contributed to the patient's clinical phenotype.