We report a case of an interstitial chromosome 20q11.21 microdeletion in a 7-year-old male child presenting with mild intellectual disability and facial dysmorphisms. Array comparative genomic hybridization (CGH) has shown that the deletion resulted in the loss of 68 genes, among which 5 genes (COX4I2, MYLK2, ASXL1, DNMT3B, and SNTA1) are disease causing. The size of the deletion was estimated to span 2.6？Mb. Only three cases of deletions encompassing this chromosomal region have been reported. The phenotype of the index patient was found to resemble the mildest cases of Bohring-Opitz syndrome that is caused by ASXL1 mutations. An in silico evaluation of the deleted genomic region has shown that benign genomic variations have never been observed to affect the ASXL1 gene, in contrast to the other disease-causing genes. As a result, it was suggested that ASXL1 loss is likely to be the main cause of the phenotypic manifestations. The present case report indicates that a loss of the disease-causing gene can produce a milder phenotype of a single gene condition. 1. Introduction The application of array comparative genomic hybridization (CGH) in clinical cytogenetics has significantly increased the diagnostic yield [1, 2]. Moreover, studying genome variations in neurobehavioral diseases using array CGH has promoted the identification of new causative submicroscopic chromosome imbalances in the clinical population [2, 3]. As a result, array CGH molecular cytogenetic analysis has become almost indispensable in children suffering from intellectual disability and related neurobehavioral problems [1–3]. Performing a similar study in the Russian cohort of children with intellectual disability and congenital malformations (for details see [4]), we have identified an interstitial 20q11.21 microdeletion in a 7-year-old male child presenting with mild intellectual disability and facial dysmorphisms. According to the available literature, only three cases of chromosome 20 deletions encompassing the same chromosomal region (excluding somatic chromosome rearrangements associated with malignant pathology) have been reported and only two cases of interstitial deletions involving 20q11.21 were previously characterized by array CGH [5–7]. 2. Case Presentation and Methods 2.1. Clinical Description A 7-year-old male child was referred to molecular cytogenetic analysis, because of intellectual disability and facial dysmorphisms. He was born at 39 weeks of gestation to a 25-year-old mother and 28-year-old father. The couple is healthy and unrelated, having a history of a previous
References
[1]
L. G. Shaffer and B. A. Bejjani, “Medical applications of array CGH and the transformation of clinical cytogenetics,” Cytogenetic and Genome Research, vol. 115, no. 3-4, pp. 303–309, 2006.
[2]
B. A. Bejjani and L. G. Shaffer, “Clinical utility of contemporary molecular cytogenetics,” Annual Review of Genomics and Human Genetics, vol. 9, pp. 71–86, 2008.
[3]
I. Y. Iourov, S. G. Vorsanova, and Y. B. Yurov, “Molecular cytogenetics and cytogenomics of brain diseases,” Current Genomics, vol. 9, no. 7, pp. 452–465, 2008.
[4]
I. Y. Iourov, S. G. Vorsanova, O. S. Kurinnaia, M. A. Zelenova, A. P. Silvanovich, and Y. B. Yurov, “Molecular karyotyping by array CGH in a Russian cohort of children with intellectual disability, autism, epilepsy and congenital anomalies,” Molecular Cytogenetics, vol. 5, no. 1, article 46, 2012.
[5]
P. Calllier, L. Faivre, N. Marle et al., “Major feeding difficulties in the first reported case of interstitial 20q11.22-q12 microdeletion and molecular cytogenetic characterization,” The American Journal of Medical Genetics A, vol. 140, no. 17, pp. 1859–1863, 2006.
[6]
M. A. Iqbal and M. Al-Owain, “Interstitial del(20)(q11.2q12)—clinical and molecular cytogenetic characterization,” The American Journal of Medical Genetics A, vol. 143, no. 16, pp. 1880–1884, 2007.
[7]
Y. Hiraki, A. Nishimura, M. Hayashidani et al., “A de novo deletion of 20q11.2-q12 in a boy presenting with abnormal hands and feet, retinal dysplasia, and intractable feeding difficulty,” The American Journal of Medical Genetics A, vol. 155, no. 2, pp. 409–414, 2011.
[8]
I. Y. Iourov, S. G. Vorsanova, E. A. Kirillova, and Y. B. Yurov, “First case of del(1)(p36.2p33) in a fetus delivered stillborn,” Prenatal Diagnosis, vol. 26, no. 11, pp. 1092–1093, 2006.
[9]
M. Kirchhoff, H. Rose, and C. Lundsteen, “High resolution comparative genomic hybridisation in clinical cytogenetics,” Journal of Medical Genetics, vol. 38, no. 11, pp. 740–744, 2001.
[10]
D. Caserta, M. Benkhalifa, M. Baldi, F. Fiorentino, M. Qumsiyeh, and M. Moscarini, “Genome profiling of ovarian adenocarcinomas using pangenomic BACs microarray comparative genomic hybridization,” Molecular Cytogenetics, vol. 1, article 10, 2008.
[11]
M. L. Slovak, D. D. Smith, V. Bedell et al., “Assessing karyotype precision by microarray-based comparative genomic hybridization in the myelodysplastic/myeloproliferative syndromes,” Molecular Cytogenetics, vol. 3, no. 1, article 23, 2010.
[12]
A. Hoischen, B. W. M. van Bon, B. Rodríguez-Santiago et al., “De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome,” Nature Genetics, vol. 43, no. 8, pp. 729–731, 2011.
[13]
I. Y. Iourov, S. G. Vorsanova, and Y. B. Yurov, “Somatic genome variations in health and disease,” Current Genomics, vol. 11, no. 6, pp. 387–396, 2010.
