Potential Biomarkers for Intellectual Disability: A Gipsy Family Study Aureli A 1 , Del Beato T 1 , Sebastiani P 1 , Di Rocco M 1 , Marimpietri AE 2 , Graziani A 2 , Sechi E 2 and Di Loreto S 1* 1 Institute of Translational Pharmacology, National Council of Research, L’Aquila, Italy 2 Childhood and Adolescence Neuropsychiatric Clinic, University of L’Aquila, ASL n. 4, L’Aquila, Italy * Corresponding author: Silvia Di Loreto, Institute of Translational Pharmacology, National Council of Research, L’Aquila, Italy, Tel: +39 0862 318843; Fax: +39 0862 320750; E-mail: silvia.diloreto@cnr.it Rec Date: September 15, 2014, Acc Date: November 13, 2014, Pub Date: November 18, 2014 Copyright: © 2014, Aureli A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Intellectual disability (ID) is frequently due to the synergic action of environmental and genetic factors. Here we describe the particular case of three Gipsy Italian siblings, fifteen, twelve and eleven years old, with ID. Genetic analysis stated that the parents are not consanguineous, and no human leukocyte antigen (HLA) alleles related to autism and/or other neurological disorders are present in the 3 ID patients. Instead, a positive association of ID with brain derived neurotrophic factor (BDNF) (Val66Met and C270T), IL6 (-174) and interleukin 1receptor antagonist (IL1RA) mspa 11100 polymorphisms was demonstrated in these three ID patients. Moreover, serum levels of interleukin 1beta (IL1β), interleukin 6 (IL6) were significantly different between the three patients and controls. Keywords: Intellectual disability; Polymorphism; Cytokine; HLA; Neurotrophic factor Introduction Several genes are involved in ID etiology but the mechanisms by which these candidates regulate cognitive function remain poorly understood [1,2]. Cytokines play a central role in CNS functions and, some of them such as IL-1beta and IL-6 have been associated with cognitive decline and dementia [3,4] and are released during neuronal activity, playing a key role in regulating the strength of synaptic [5,6]. Peripheral expression of cytokines can influence both in pathological and physiological conditions, the hippocampus-related memory and synaptic plasticity [7-9] and there is growing evidence that single nucleotide polymorphisms (SNPs) regulate theirs expression [10,11]. Several polymorphisms of BDNF gene have been described and in our previous study a positive association between ID and two BDNF SNPs was demonstrated (Val66Met and C270T) [12]. Current research increasingly also demonstrates a role of the HLA proteins in the functional interactions of neural cells, in CNS development [13], and even in neurological disorders [14]. The phenylketonuria (PKU), a defect in the hepatic enzyme phenylalanine hydroxylase (PAH), is an inherited disorder that induces delayed mental and social skills. A higher incidence of PKU was demonstrated in Gypsies than in other populations [15], and two missense mutations have been identified in the PAH gene of an Italian PKU patient [16]. Herein, we report the particular case of three Gipsy ID siblings in which functional cytokine gene polymorphisms, serum levels of cytokines, HLA class I and II allele polymorphisms, BDNF gene polymorphisms and two PAH missense mutations have been studied. Case Report Three children belonging to a Gipsy family living in the area of the coast of the Adriatic Sea were enrolled at the Department of Neuropsychiatric Disorders of the Civil Hospital of L’Aquila, Italy (Figure 1A). Patient 1 The first patient is a female born in 1999 without complications after a normal pregnancy. From birth, her psychomotor development was delayed, and included feeding problems. She was able to walk at the age of 18 months. At 5 years old she spoke only a few words and started intensive linguistic training. A severe intellectual disability was diagnosed (IQ 35). She is described as an easily irascible although quite sociable child. Patient 2 The other female, born in 2002 after an uneventful pregnancy, developed critical anaemia after the birth and received blood transfusions. She began walking at 15 months old and a delay in language development and in the control of the sphincters was reported. Severe intellectual disability (IQ 34) was noticed early on. Some spread electric anomalies, particularly in the frontal lobe area, were observed by her electroencephalogram. She is shy and unable to integrate with peers. Patient 3 The younger affected brother was born in 2003 by caesarean section. The same psychomotor development pattern seen in his affected sisters was present. His speech was delayed and he started to speak at 3 years old. A mild intellectual disability was diagnosed (IQ 59). He is short-tempered and does not socialize easily. According to Diagnostic and Statistical Manual of Mental Disorders- IV Edition (DSM-IV) criteria, to access ID diagnosis Wechsler Intelligence Scale for Children-III (WISC-III), a standardized test of intellectual aptitude for children between ages 6 and 16 years, and the Vineland Adaptive Behaviour Scales (VABS) were administrated. The WISC-III subscales are used to generate four composite scores: verbal comprehension, perceptual reasoning, working memory, and processing speed. The VABS is a widely used tool for assessing an individual’s ability to care for one’s self personally and socially. The Child Behaviour CheckList (CBCL), a parent-report Hereditary Genetics: Current Research Aureli, et al., Hereditary Genet 2014, 3:3 http://dx.doi.org/10.4172/2161-1041.1000138 Case Report Open Access Hereditary Genet ISSN:2161-1041 HGCR, an open access journal Volume 3 • Issue 3 • 1000138