| Title | Claps | Level | Year | L/Y |
|---|---|---|---|---|
|
Schizophrenia in a patient with subtelomeric duplication of chromosome 22q
10 auth. P. Failla, Carrado Romano, A. Alberti, A. Vasta, S. Buono, L. Castiglia, ...
To the Editor: Schizophrenia is a common and severe psychiatric condition. To date, only a few genes have been involved as risk factors (1). Chromosomal rearrangements associated with this disorder are a valuable resource (2). Here, we report on a g…
To the Editor: Schizophrenia is a common and severe psychiatric condition. To date, only a few genes have been involved as risk factors (1). Chromosomal rearrangements associated with this disorder are a valuable resource (2). Here, we report on a girl with schizophrenia showing a 22q13.3-qter duplication, without any familial neuropsychiatric disease, documented by a three-generation family history. We were not able to establish a de novo origin of the duplication because the father and his parents were dead at the time of ascertainment. Developmental milestones were reached within normal range. Menarche (13 years) was the time of onset of initial behavioural problems (agitation, social closure and passivity), followed at the age of 15 years by auditory hallucinations, loss of self-control, dysfunction of self-awareness with temporary amnesia, disorientation, aggressive acting out and sleep disturbances. At the present age of 20 years, psychometric testing with Wechsler Adult Intelligence Scale-Revised shows a global intelligence quotient (IQ) of 73, a verbal IQ of 71 and a performance IQ of 80, whereas the score is 86 at Standard Progressive Matrices. The girl presents also with psychomotor restlessness and attention deficit. Ideation is severely impaired and speech is incoherent. Marked irritability, sexually related problems, unstable temper, and aggressive reaction to disappointment are also evident. General affectivity is compromised. Difficulties in accepting and following the rules in different social contexts highlight the adaptive area. Apathy and poor personal hygiene complete the clinical picture, which satisfies the Diagnostic statistical manual, 4th Ed., Text Revised (DSM IV-TR) (3) diagnostic criteria for borderline intellectual functioning and disorganized schizophrenia. The phenotype is also characterized by muscular hypotonia, microbrachycephaly (present also in the mother), hypertelorism, moderate myopia, downslanting palpebral fissures, deviation of the nasal septum, helix hyperplasia, thick lips, retrognathia, hypothenar eminence hypoplasia, scoliosis, splayfoot with valgus hallux, and joint hyperlaxity. The brain computerized tomography scan is normal. The electroencephalogram shows low-voltage sharp-wave complexes on the posterior areas of both hemispheres. A normal 46, XX karyotype from peripheral blood lymphocytes followed by a Multiprobe FISH Assay (Chromoprobe Multiprobe-T SystemCytocell Ltd, Oxford, UK) disclosed a third 22qter signal on the p arm of chromosome 22, not present in the clinically normal mother. Segregation pattern of the informative D22S1170 microsatellite revealed in our patient one maternal and two paternal alleles. The extent of the rearrangement was then assessed by array CGH assay using Human Genome CGH Microarray Kit 44B (Agilent Technologies, Palo Alto, CA), which showed a terminal 5.4 Mb duplication (Fig. 1). Among the 21 patients with terminal 22q duplications recently reviewed (4), only two (patients 2 and 3, respectively, father and son) have a duplication size comparable with that of our patient. Interestingly, this is the smallest duplication so far reported, and the patients show minor learning disabilities, psychiatric difficulties since early childhood and mild mental retardation’. The more severe degree of mental retardation, found in larger duplications, hampers the diagnosis of schizophrenia. Linkage findings for schizophrenia have been reported on chromosome 22q13 (5, 6), suggesting that one or more genes in this region could confer susceptibility to this psychiatric disorder. Among the several genes mapping there, we want to draw the attention on two of them: SHANK3 and WNT7B. The gene SHANK3 (7–9) codes for a scaffolding protein of the post-synaptic density of excitatory synapses in the mammalian brain, and its expression increases during post-natal development especially in the cerebellum and thalamus. WNT7B belongs to Wingless (Wnt) family members, secreted glycoproteins, which are intracellular signalling molecules both during neural development and in the mature nervous system (10). The Wnt signalling pathway has
Published in
Clinical Genetics
|
10
|
5 | 2007 |
Social Media Posts