J Korean Med Sci.  2008 Dec;23(6):1097-1101. 10.3346/jkms.2008.23.6.1097.

Partial Trisomy 1q41 Syndrome Delineated by Whole Genomic Array Comparative Genome Hybridization

• Shin YB
• Nam SO
• Seo EJ
• Kim HH
• Chang CL
• Lee EY
• Son HC
• Hwang SH

• KMID: 1107538
• DOI: http://doi.org/10.3346/jkms.2008.23.6.1097

Abstract

Partial trisomy 1q syndrome is a rare chromosomal abnormality. We report on a male infant with 46,XY,der(11)t(1;11)(q41;p15.5) due to unbalanced segregation of the maternal reciprocal balanced translocation 46,XX,t(1;11)(q41;p15.5). The baby presented with a mild phenotype, characterized by a triangular face, almond-shaped eyes, low ears, short stature with relatively long legs, and mild psychomotor retardation. We utilized whole genomic array comparative genome hybridization (CGH) with 4,000 selected bacterial artificial chromosomes (BACs) to define the chromosomal breakpoints and to delineate the extent of the partial trisomy in more detail. To our knowledge, this is the first case of nearly pure "partial trisomy 1q41" defined by whole genomic array CGH.

Keyword

Trisomy 1q41; Unbalanced Translocation; Partial Trisomy 1q Syndrome; Array CGH

MeSH Terms

Chromosomes, Human, Pair 1/*genetics
Chromosomes, Human, Pair 11
Comparative Genomic Hybridization
Humans
In Situ Hybridization, Fluorescence
Infant
Karyotyping
Male
Oligonucleotide Array Sequence Analysis
Phenotype
Translocation, Genetic
*Trisomy

Figure

• 

  Fig. 1 Karyotype of the proband's mother (A) and the proband (B).

• 

  Fig. 2 Ratio plots from array data for chromosomes 1 and 11 of the proband. Each ratio plot is the average of normalized data from two independent arrays. Normalized data from the array in which the test sample was labeled with Cy3 is shown in red while that with Cy5 is shown in blue. (A) Chromosome 1, showing a contiguous duplication on the q-arm. (B) Chromosome 11, showing two-clone deletions of BAC_1341 and BAC_5807 on the p-arm (arrow). The duplicated signals by array CGH in 11q12.2 were considered as copy-number variations because the same signals were also present in the array CGH of proband's mother (arrowhead).

• 

  Fig. 3 FISH analysis using BAC probes. (A) BAC_4527 (red; proximal to the interval) and BAC_7952 (green) showing translocation break region of 1q41. (B) 1q43 probe (red, BAC_4069) showed intact signals (a continuous gene rearrangement at 1q41-qter) implicating that no duplication pattern around at 1q43 of the array CGH result was false. (C) BAC_1341 and BAC_5807 (red; distal to the deletion boundary of 11p15.5) were showed a red signal loss of der(11), which confirmed the deletion pattern by the array CGH.

Reference

1. Rasmussen SA, Frias JL, Lafer CZ, Eunpu DL, Zackai EH. Partial duplication 1q: report of four patients and review of the literature. Am J Med Genet. 1990. 36:137–143.

2. Emberger W, Petek E, Kroisel PM, Zierler H, Wagner K. Clinical and molecular cytogenetic characterization of two patients with partial trisomy 1q41-qter: further delineation of partial trisomy 1q syndrome. Am J Med Genet. 2001. 104:312–318.

3. DuPont BR, Huff RW, Ridgway LE, Stratton RF, Moore CM. Prenatal diagnosis of partial trisomy 1q using fluorescent in situ hybridization. Am J Med Genet. 1994. 50:21–27.

4. Clark BJ, Lowther GW, Lee WR. Congenital ocular defects associated with an abnormality of the human chromosome 1: trisomy 1q32-qter. J Pediatr Ophthalmol Strabismus. 1994. 31:41–45.

5. Duba HC, Erdel M, Loffler J, Bereuther L, Fischer H, Utermann B, Utermann G. Detection of a de novo duplication of 1q32-qter by fluorescence in situ hybridisation in a boy with multiple malformations: further delineation of the trisomy 1q syndrome. J Med Genet. 1997. 34:309–313.

6. Chia NL, Bousfield LR, Poon CC, Trudinger BJ. Trisomy (1q)(q42----qter): confirmation of a syndrome. Clin Genet. 1988. 34:224–229.

7. Verschuuren-Bemelmans CC, Leegte B, Hodenius TM, Cobben JM. Trisomy 1q42--> qter in a sister and brother: further delineation of the "trisomy 1q42--> qter syndrome". Am J Med Genet. 1995. 58:83–86.

8. Concolino D, Cinti R, Ferraro L, Moricca MT, Strisciuglio P. Partial trisomy 1(q42-->qter): a new case with a mild phenotype. J Med Genet. 1998. 35:75–77.

9. Pinkel D, Albertson DG. Comparative genomic hybridization. Annu Rev Genomics Hum Genet. 2005. 6:331–354.

10. Moon HJ, Yim SV, Lee WK, Jeon YW, Kim YH, Ko YJ, Lee KS, Lee KH, Han SI, Rha HK. Identification of DNA copy-number aberrations by array-comparative genomic hybridization in patients with schizophrenia. Biochem Biophys Res Commun. 2006. 344:531–539.

11. Park SJ, Jeong SY, Kim HJ. Y chromosome loss and other genomic alterations in hepatocellular carcinoma cell lines analyzed by CGH and CGH array. Cancer Genet Cytogenet. 2006. 166:56–64.