Chromosomal 16p microdeletion in Rubinstein-Taybi syndrome detected by oligonucleotide-based array comparative genomic hybridization: a case report
Tóm tắt
Chromosomal aberrations of chromosome 16 are uncommon and submicroscopic deletions have rarely been reported. At present, a cytogenetic or molecular abnormality can only be detected in 55% of Rubinstein-Taybi syndrome patients, leaving the diagnosis in 45% of patients to rest on clinical features only. Interestingly, this microdeletion of 16 p13.3 was found in a young child with an unexplained syndromic condition due to an indistinct etiological diagnosis. To the best of our knowledge, no evidence of a microdeletion of 16 p13.3 with contiguous gene deletion, comprising cyclic adenosine monophosphate-response element-binding protein and tumor necrosis factor receptor-associated protein 1 genes, has been described in typical Rubinstein-Taybi syndrome. We present the case of a three-year-old Malaysian Chinese girl with a de novo microdeletion on the short arm of chromosome 16, identified by oligonucleotide array-based comparative genomic hybridization. Our patient showed mild to moderate global developmental delay, facial dysmorphism, bilateral broad thumbs and great toes, a moderate size atrial septal defect, hypotonia and feeding difficulties. A routine chromosome analysis on 20 metaphase cells showed a normal 46, XX karyotype. Further investigation by high resolution array-based comparative genomic hybridization revealed a 120 kb microdeletion on chromosomal band 16 p13.3. A mutation or abnormality in the cyclic adenosine monophosphate-response element-binding protein has previously been determined as a cause of Rubinstein-Taybi syndrome. However, microdeletion of 16 p13.3 comprising cyclic adenosine monophosphate-response element-binding protein and tumor necrosis factor receptor-associated protein 1 genes is a rare scenario in the pathogenesis of Rubinstein-Taybi syndrome. Additionally, due to insufficient coverage of the human genome by conventional techniques, clinically significant genomic imbalances may be undetected in unexplained syndromic conditions of young children. This case report demonstrates the ability of array-based comparative genomic hybridization to offer a genome-wide analysis at high resolution and provide information directly linked to the physical and genetic maps of the human genome. This will contribute to more accurate genetic counseling and provide further insight into the syndrome.
Tài liệu tham khảo
Rubinstein JH, Taybi H: Broad thumbs and toes and facial abnormalities. A possible mental retardation syndrome. Am J Dis Child. 1963, 105: 588-608.
Hennekam RCM, Stevens CA, Van de Kamp JJ: Etiology and recurrence risk in Rubinstein-Taybi syndrome. Am J Med Genet Suppl. 1990, 6: 56-64.
Hennekem RCM: Rubinstein-Taybi syndrome. Eur J Hum Genet. 2006, 14: 981-985. 10.1038/sj.ejhg.5201594.
Coupry I, Roudaut C, Stef M, Delrue MA, Marche M, Burgelin I, Taine L, Cruaud C, Lacombe D, Arveiler B: Molecular analysis of the CBP gene in 60 patients with Rubinstein-Taybi syndrome. J Med Genet. 2002, 39: 416-421.
Bartsch O, Schmidt S, Richter M, Morlot S, Seemanová E, Wiebe G, Rasi S: DNA sequencing of CREBBP demonstrates mutations in 56% of patients with Rubinstein-Taybi syndrome (RSTS) and in another patient with incomplete RSTS. Hum Genet. 2005, 117: 485-493. 10.1007/s00439-005-1331-y.
Roelfsema JH, White SJ, Ariyürek Y, Bartholdi D, Niedrist D, Papadia F, Bacino CA, Dunnen JT, van Ommen GJB, Breuning MH, Hennekem RC, Peters DJM: Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet. 2005, 76: 572-580. 10.1086/429130.
Bartsch O, Wagner A, Hinkel GK, Krebs P, Stumm M, Schmalenberger B, Böhm S, Majewski F: FISH studies in 45 patients with Rubinstein-Taybi syndrome: deletions associated with polysplenia, hypoplastic left heart and death in infancy. Eur J Hum Genet. 1999, 7: 748-756. 10.1038/sj.ejhg.5200378.
Coupry I, Monnet L, Attia AA, Taine L, Lacombe D, Arveiler B: Analysis of CREBBP gene deletions in Rubinstein-Taybi syndrome patients using real-time quantitative PCR. Hum Mutat. 23: 278-284.
Petrij F, Dauwerse HG, Blough RI, Giles RH, van der Smagt JJ, Wallerstein R, Maaswinkel-Mooy PD, van Karnebeek CD, van Ommen GJB, van Haeringen A, Rubinstein JH, Saal HM, Hennekam RC, Peters DJM, Breuning MH: Diagnostic analysis of the Rubinstein-Taybi syndrome: five cosmids should be used for microdeletion detection and low number of protein truncating mutations. J Med Genet. 2000, 37: 168-176. 10.1136/jmg.37.3.168.
Hui Tsai AC, Dossett CJ, Walton CS, Cramer AE, Eng PA, Nowakowska BA, Pursley AN, Stankiewicz P, Wiszniewska J, Cheung SW: Exon deletions of the EP300 and CREBBP genes in two children with Rubinstein-Taybi syndrome detected by aCGH. Eur J Hum Genet. 2010, 19: 43-49.
Chen B, Piel WH, Gui L, Bruford E, Monteiro A: The HSP90 family of genes in the human genome: insights into their divergence and evolution. Genomics. 2005, 86: 627-637. 10.1016/j.ygeno.2005.08.012.
Bartsch O, Rasi S, Delicado A, Dyack S, Neumann LM, Eva Seemanová E, Marianne Volleth M, Haaf T, Kalscheuer VM: Evidence for a new contiguous gene syndrome, the chromosome 16 p13.3 deletion syndrome alias severe Rubinstein-Taybi syndrome. Hum Genet. 2006, 120: 179-186. 10.1007/s00439-006-0215-0.
Wójcik C, Volz K, Ranola M, Kitch K, Karim T, O'Neil J, Smith J, Torres-Martinez W: Rubinstein-Taybi syndrome associated with Chiari type I malformation caused by a large 16 p13.3 microdeletion: a contiguous gene syndrome?. Am J Med Genet. 2010, 479-483. 152A
Mijuskovic Z, Karadaglic D, Stojanov L: Rubinstein-Taybi Syndrome Last Updated. e-medicine [Online]. 2006, http://www.emedicine.com/derm/topic711.htm
Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. http://decipher.sanger.ac.uk/