Pervasive Developmental Disorders and GABAergic System in Patients With Inverted Duplicated Chromosome 15

Abstract

Pervasive developmental disorders are characterized by severe, pervasive impairment in several areas of development, with distorted communication skills and stereotypical behavior. Pervasive developmental disorders have a heterogeneous etiology related to brain damage, familial affective psychopathology, chromosomal abnormalities, or dysfunction of neuromodulators. Recently, it has been suggested that the GABRB3 gene, located within chromosome 15q11-13, is a candidate for pervasive developmental disorder. In inverted duplicated chromosome 15 syndrome, in which there is a small marker chromosome derived from inversion and duplication of the chromosome 15q11-q13 region, all patients present with pervasive developmental disorder. To further investigate a possible involvement of the gamma-aminobutyric acid (GABA)ergic system in the inverted duplicated chromosome 15 syndrome, we evaluated plasma levels of GABA and diazepam binding inhibitor in 6 patients with inverted duplicated chromosome 15 and in 8 subjects not affected by neurologic disease. Our findings do not seem to support this hypothesis as no significant differences were found in the GABA and diazepam binding inhibitor plasma levels between patients with inverted duplicated chromosome 15 and controls, but we must consider the possibility that a genetic abnormality of the GABA(A) receptor could be present in patients with inverted duplicated chromosome 15 and still not be reflected in an alteration in either GABA or diazepam binding inhibitor levels in plasma.

Overlap With the Autism Spectrum in Young Children With Williams Syndrome

“…Overlaps with the autism spectrum have been identified for children with a wide variety of genetically-based neurodevelopmental disorders including Down syndrome (26), Fragile-X syndrome (27) Angelman syndrome (28), Inverted Duplication 15 syndrome (29) and others. The study of ASD characteristics in populations with known genetic etiologies has grown in an effort to better understand the pathophysiology of ASD.…”

A capillary liquid chromatographic/tandem mass spectrometric method for the quantification of γ-aminobutyric acid in human plasma and cerebrospinal fluid

“…From these analyses, plasma GABA level in healthy subjects was found to be 98.6 ± 33.9 ng/mL (mean ± S.D., n = 12), which is statistically in accordance with the result reported recently by Shiah et al [6] (126.9 ± 63.8 ng/mL, mean ± S.D., n = 10). However, this number is much higher than some other literature values (12.5-18.8 ng/mL) [19][20][21]. After carefully reading these papers, we found that the measurements of plasma GABA in all of these works were carried out following an HPLC/fluorescence procedure described by Hare and Maynam [25].…”

“…However, the signal was too weak to make any quantitative analysis [14]. Although the HPLC-MS method was used for the determination of GABA in rat brain tissues, it had a detection limit of 2.5 ± 0.3 g/mL [18], Obviously, this method won't be sensitive enough for quantifying GABA in human plasma, in which the GABA level is consistently found to be below 150 ng/mL [4,6,[19][20][21], HPLC coupled to mass spectrometry (MS) has become a popular analytical technique. However, the sensitivity of an HPLC-MS combination is often lackluster compared with fluorescence detection, particularly when standard-size HPLC columns (4 mm i.d.)…”

Autistic-like symptomatology in Prader-Willi syndrome: A review of recent findings

“…An understanding of the role of 15q11-q13 in social disability is further complicated by the identifi cation of a putative association between common alleles of the nonimprinted gene (GABRB3) and autism, although these fi ndings have not yet been convincingly replicated [ 45 ]. Finally, recent evidence points to dysregulation of gene expression in the 15q11-13 region in Angelman's syndrome, Rett syndrome, and autism [ 8 , 9 ].…”