Analysis of Copy Number Variations in Patients with Autism Using Cytogenetic and MLPA Techniques: Report of 16p13.1p13.3 and 10q26.3 Duplications

Document Type : Original Article

Authors
Roshanak Vameghi 1
Roxana Kariminejad 2
Hossein Darvish 3
Susan Banihashemi 4
Mahboubeh Firouzkouhi Moghaddam 5 , 6
Peyman Jamali 7
Hassan Farbod Mofidi Tehrani 8
Hossein Dehghani 4
Mohammad Reza Raeisoon 9
Mehrnaz Narooie-Nejad 10
Javad Jamshidi 11
Abbas Tafakhori 12
Saeid Sadabadi 13
Farkhondeh Behjati 4
1 Pediatric Neurorehabilitation Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
2 Kariminejad- Najmabadi Pathology and Genetics Center, Tehran, Iran
3 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
5 Child and Adolescent Psychiatry Department, Zahedan University of Medical Sciences, Zahedan, Iran
6 Research Center for Children and Adolescents Health, Zahedan University of Medical Sciences, Zahedan, Iran
7 Shahroud Welfare Organization, Shahroud, Iran
8 Health Psychology Department, Edalat University, Tehran, Iran
9 Psychiatry and Behavioral Science Research Center, Department of Social Medicine, Medicine Faculty, Birjand University of Medical Sciences, Birjand, Iran
10 Genetics of Non- Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
11 Non-Communicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran
12 Department of Neurology, School of Medicine, Imam Khomeini Hospital and Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran
13 Bahar Education and Rehabilitation Center for the handicapped, Tehran, Iran
10.22088/acadpub.BUMS.5.4.236
Abstract
Autism is a common neuropsychiatric disorder affecting 1 in 68 children. Copy number variations (CNVs) are
known to be major contributors of autism spectrum disorder (ASD). There are different whole genome or
targeted techniques to identify CNVs in the patients including karyotyping, multiplex ligation-dependent probe
amplification (MLPA) and array CGH. In this study, we used karyotyping and MLPA to detect CNVs in 50
Iranian patients with autism. GTG banding and 4 different MLPA kits (2 subtelomeric and 2 autism kits) were
utilized. To elevate our detection rate, we selected the sporadic patients who had additional clinical features
including intellectual disability, seizure, attention deficit hyperactivity disorder, and abnormal head
circumference. Two out of 50 patients (4%) showed microscopic chromosome abnormalities and 5 out of 50
(10%) demonstrated copy number gains or losses using MLPA kits. Including one overlapping result between
karyotype and MLPA techniques, our overall detection rate was 6 out of 50 (12%). Three out of 6 CNVs were de novo and three others were paternally inherited. Two of CNVs detected by karyotyping and MLPA tests were
16p13.1q13.3 and 10q26.3 duplications, respectively. For these two CNVs genotype and phenotype of the
patients were compared with other studies. Although the pathogenicity of cytogenetic results was certain, most
of MLPA results needed to be better refined using other more accurate techniques such as array CGH. Our
findings suggest that it might be possible to obtain some useful information using MLPA technique but it cannot
be used as a single diagnostic tool for the autism.
Keywords
Autism
MLPA
cytogejnetic
16p13.1p13.3 duplication
10q26.3 duplication