The molecular karyotyping of undifferentiated forms of intellectual disabilities: from chromosomal mutations to identification of pathogenic genes
https://doi.org/10.1234/XXXX-XXXX-2016-4-46-49
Abstract
Introduction. One of the genetic causes of intellectual disabilities (ID) is copy number variation (CNV). Despite the fact that for some variations an association with known syndromes has been shown, most of them are rare. Usually CNVs involve extended regions, including several genes. In some cases CNVs include single genes, what enables to directly link a change of their dose with clinical abnormalities observed in a patient. Aim. This work aims to characterize structural genomic variation in patients with ID and map candidate genes. Materials and methods. Using Agilent 44K and 60K arrays the molecular karyotyping for 136 children of 3-17 years old with developmental delay, ID and dysmorphic features was performed. Results. Eighty-seven individuals (64%) had normal karyotype or benign CNVs. Known microdeletion or microduplication syndromes were identified in 18 patients (13%). In the remaining 31 children (23%) potentially pathogenic mutations were found. For 15q24 and 16p11.2 microdeletion syndromes, diagnosed in two and three patients, respectively, using the literature data the minimal deleted regions and candidate genes within them were identified. In two families the reciprocal microdeletion and miproduplication of single CNTN6 gene were found. This gene is expressed in the brain and, therefore, is a candidate for ID. Conclusions. aCGH-analysis is an effective method for genetic diagnosis, which, when mutations in single genes are detected, allows identification of new candidate genes for intellectual disability.
About the Authors
A. A. Kashevarova
Research Institute of Medical Genetics; National Research Tomsk State University
Russian Federation
Russian Federation
N. A. Skryabin
Research Institute of Medical Genetics; National Research Tomsk State University
Russian Federation
Russian Federation
M. E. Lopatkina
Research Institute of Medical Genetics
Russian Federation
Russian Federation
O. A. Salyukova
Research Institute of Medical Genetics; Siberian State Medical University
Russian Federation
Russian Federation
M. N. Filimonova
Research Institute of Medical Genetics
Russian Federation
Russian Federation
O. V. Lezhnina
Research Institute of Medical Genetics
Russian Federation
Russian Federation
A. R. Shorina
State Novosibirsk Regional Clinical Diagnostic Center; State Novosibirsk Regional Children’s Psycho-Neurological Center
Russian Federation
Russian Federation
A. B. Maslennikov
State Novosibirsk Regional Clinical Diagnostic Center
Russian Federation
Russian Federation
L. P. Nazarenko
Research Institute of Medical Genetics; Siberian State Medical University
Russian Federation
Russian Federation
V. . Culic
University Hospital Centre
Russian Federation
Russian Federation
I. N. Lebedev
Research Institute of Medical Genetics; Siberian State Medical University; National Research Tomsk State University
Russian Federation
Russian Federation
References
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Review
For citations:
Kashevarova A.A., Skryabin N.A., Lopatkina M.E., Salyukova O.A., Filimonova M.N., Lezhnina O.V., Shorina A.R., Maslennikov A.B., Nazarenko L.P., Culic V., Lebedev I.N. The molecular karyotyping of undifferentiated forms of intellectual disabilities: from chromosomal mutations to identification of pathogenic genes. Medical Genetics. 2016;15(4):46-49. (In Russ.) https://doi.org/10.1234/XXXX-XXXX-2016-4-46-49
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