Inheritance of a Balanced t(12;20)(q24.33;p12.2) and Unbalanced der(13)t(7;13)(p21.3;q33.2) from a Maternally Derived Double Balanced Translocation Carrier

Abstract

We report a 4-month-old male proband with a history of prominent forehead, hypertelorism, ear abnormalities, micrognathia, hypospadias, and multiple cardiac abnormalities. Initial microarray analysis detected a concurrent 7p21.3-p22.3 duplication and 13q33.2-q34 deletion indicating an unbalanced rearrangement. However, subsequent conventional cytogenetic studies only revealed what appeared to be a balanced t(12;20)(q24.33;p12.2). Fluorescence in situ hybridization (FISH) using chromosome-specific subtelomere probes confirmed the presence of an unbalanced der(13)t(7;13)(p21.3;q33.2) and balanced t(12;20)(q24.33;p12.2), both of maternal origin. In addition to our unique clinical findings, this case highlights the benefits and limitations of both conventional cytogenetic studies and microarray analysis and how FISH complements each methodology.

Keywords

7p21.3-p22.3 duplication - 13q33.2-q34 deletion - unbalanced translocation - double balanced translocation carrier - fluorescence in situ hybridization - array comparative genomic hybridization

• References

• 1 Chen CP, Wu PC, Lin CJ. , et al. Balanced reciprocal translocations detected at amniocentesis. Taiwan J Obstet Gynecol 2010; 49 (04) 455-467
• 2 Gardner RJM, Sutherland GR, Shaffer LG. Chromosome Abnormalities and Genetic Counseling. 4th ed. New York City: Oxford University Press; 2012
• 3 Redin C, Brand H, Collins RL. , et al. The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies. Nat Genet 2017; 49 (01) 36-45
• 4 Ordulu Z, Kammin T, Brand H. , et al. Structural chromosomal rearrangements require nucleotide-level resolution: lessons from next-generation sequencing in prenatal diagnosis. Am J Hum Genet 2016; 99 (05) 1015-1033
• 5 Bowser-Riley SM, Griffiths MJ, Creasy MR. , et al. Are double translocations double trouble?. J Med Genet 1988; 25 (05) 326-331
• 6 Simioni M, Steiner CE, Gil-da-Silva-Lopes VL. De novo double reciprocal translocations in addition to partial monosomy at another chromosome: a very rare case. Gene 2015; 573 (01) 166-170
• 7 Uysal A, Uludağ A, Sılan F, Erçelen N, Zafer C, Ozdemir O. Double translocation: an interesting family history. Balkan J Med Genet 2013; 16 (01) 77-80
• 8 Martin CL, Warburton D. Detection of chromosomal aberrations in clinical practice: from karyotype to genome sequence. Annu Rev Genomics Hum Genet 2015; 16: 309-326
• 9 Treff NR, Zimmerman RS. Advances in preimplantation genetic testing for monogenic disease and aneuploidy. Annu Rev Genomics Hum Genet 2017; DOI: 10.1146/annurev-genom-091416-035508.
• 10 Caselli R, Ballarati L, Vignoli A. , et al. 7p22.1 microduplication syndrome: clinical and molecular characterization of an adult case and review of the literature. Eur J Med Genet 2015; 58 (11) 578-583
• 11 Cox DM, Butler MG. A case of the 7p22.2 microduplication: refinement of the critical chromosome region for 7p22 duplication syndrome. J Pediatr Genet 2015; 4 (01) 34-37
• 12 Pebrel-Richard C, Rouzade C, Kemeny S. , et al. Refinement of the critical region in a new 7p22.1 microduplication syndrome including craniofacial dysmorphism and speech delay. Am J Med Genet A 2014; 164A (11) 2964-2967
• 13 Preiksaitiene E, Kasnauskiene J, Ciuladaite Z, Tumiene B, Patsalis PC, Kučinskas V. Clinical and molecular characterization of a second case of 7p22.1 microduplication. Am J Med Genet A 2012; 158A [phone]
• 14 Ronzoni L, Grassi FS, Pezzani L. , et al. 7p22.1 microduplication syndrome: Refinement of the critical region. Eur J Med Genet 2017; 60 (02) 114-117
• 15 Andresen JH, Aftimos S, Doherty E, Love DR, Battin M. 13q33.2 deletion: a rare cause of ambiguous genitalia in a male newborn with growth restriction. Acta Paediatr 2010; 99 (05) 784-786
• 16 Huang C, Yang YF, Yin N. , et al. Congenital heart defect and mental retardation in a patient with a 13q33.1-34 deletion. Gene 2012; 498 (02) 308-310
• 17 McMahon CJ, Breathnach C, Betts DR, Sharkey FH, Greally MT. De novo interstitial deletion 13q33.3q34 in a male patient with double outlet right ventricle, microcephaly, dysmorphic craniofacial findings, and motor and developmental delay. Am J Med Genet A 2015; 167A [phone]
• 18 Walczak-Sztulpa J, Wisniewska M, Latos-Bielenska A. , et al. Chromosome deletions in 13q33-34: report of four patients and review of the literature. Am J Med Genet A 2008; 146A [phone]
• 19 Yang YF, Ai Q, Huang C. , et al. A 1.1Mb deletion in distal 13q deletion syndrome region with congenital heart defect and postaxial polydactyly: additional support for a CHD locus at distal 13q34 region. Gene 2013; 528 (01) 51-54