Taiwan J Obstet Gynecol • June 2010 • Vol 49 • No 2 188
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Chih-Ping Chen1,2,3,4,5,6*, Chyi-Chyang Lin7, Yi-Ning Su8, Fuu-Jen Tsai4,7,9, Ju-Ting Chen2, Schu-Rern Chern2, Chen-Chi Lee1, Dai-Dyi Town1, Li-Feng Chen1, Pei-Chen Wu1, Wayseen Wang2,10
Departments of 1Obstetrics and Gynecology and 2Medical Research, Mackay Memorial Hospital, Taipei, 3Department of Biotechnology, Asia University, 4School of Chinese Medicine, College of Chinese Medicine, China Medical
University, Taichung, 5Institute of Clinical and Community Health Nursing, National Yang-Ming University, 6Department of
Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, 7Department of Medical Research, China Medical University Hospital, Taichung, 8Department of Medical Genetics, National Taiwan University Hospital,
Taipei, 9Department of Medical Genetics, China Medical University Hospital, Taichung, and
10Department of Bioengineering, Tatung University, Taipei, Taiwan.
SUMMARY
Objective:Prenatal diagnosis of small supernumerary marker chromosomes (sSMC) gives rise to difficulties in genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping, fluorescence
in situ hybridization, multicolor-fluorescence in situ hybridization, or array-comparative genomic hybridization to
iden-tify the nature of the aberrant chromosome. We report such a case associated with a reciprocal translocation.
Materials, Methods and Results:A 36-year-old woman, gravida 7, para 1, abortus 5, was referred for amniocente-sis at 18 weeks of gestation because of advanced maternal age. Amniocenteamniocente-sis revealed a reciprocal translocation between chromosomes 17q and 18q and an sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2), +mar. Chromosome preparations from blood lymphocytes revealed that she had the same reciprocal translocation and sSMC. Spectral karyotyping showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18. The derivative chromosome 17 had positive 17p terminal (17pTEL) and chromosome 17 centromeric (cep17) signals but did not have a positive chro-mosome 18 centromeric signal (cep18). The derivative chrochro-mosome 18 had positive 18p terminal (18pTEL), chromosome 18 centromeric (cep18) and cep17 signals. The sSMC had only a positive cep18 signal. These find-ings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromosome 18. The karyotype of the fetus was thus 47,XY,t(17;18)(q11.1;q11.2),+mar.ish der(17)t(17;18)(q11.1;q11.2)(17pTEL+,D17Z1+),der(18)t(17;18)(q11.1;q11.2)(18pTEL+,D18Z1+,D17Z1+), + der(18)(D18Z1+). Oligonucleotide-based array comparative genomic hybridization demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18.
Conclusion:Our case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 without phenotypic consequences. [Taiwan J Obstet Gynecol 2010;49(2):188–191]
*Correspondence to: Dr Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan.
E-mail: [email protected] Accepted: November 26, 2009
Taiwan J Obstet Gynecol • June 2010 • Vol 49 • No 2 189 A Small Supernumerary Marker From Chromosome 18
Introduction
Prenatal diagnosis of small supernumerary marker chro-mosomes (sSMCs) results in difficulties with respect to genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping (SKY), fluo-rescence in situ hybridization (FISH), multicolor-FISH (M-FISH), centromere-specific multicolor-FISH (cenM-FISH) and subcentromeric multicolor-FISH (subcenM-FISH), or array comparative genomic hybridization (aCGH) to identify the nature of the aberrant chromo-some [1–4]. sSMCs are defined as structurally abnormal chromosomes that cannot be identified or character-ized by conventional banding cytogenetics and are gen-erally equal in size or smaller than chromosome 20 [5–7]. sSMCs are present in 0.044% of newborn infants and in 0.075% of prenatal cases [4,5,7,8]. About 70% of sSMCs arise de novo [8], around 70% of sSMCs are derived from acrocentric chromosomes [5,9], and ap-proximately 70% of cases from de novo sSMCs have no phenotypic effects [4].
Materials, Methods and Results
A 36-year-old woman, gravida 7, para 1, was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. The woman was phenotypi-cally normal but had experienced five spontaneous abortions and delivered a phenotypically normal son.
Amniocentesis revealed a reciprocal translocation be-tween chromosome arms 17q and 18q and a sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2),+ mar (Figure 1). Chromosome preparations of blood lym-phocytes from the woman revealed that she had the same reciprocal translocation and sSMC. At 38 weeks of gestation, the woman delivered a healthy 2,656 g male baby without any phenotypic abnormality. The sSMC and the derivative chromosome were character-ized by SKY using 24-color SKY probes (Applied Spec-tral Imaging, Carlsbad, CA, USA) and FISH using a 17p-specific telomeric probe (17pTEL), chromosome 17 centromeric probe (cep17), 18p-specific telomeric probe (18pTEL), and chromosome 18 centromeric probe (cep18) (TelVysion; Vysis, Downers Groove, IL, USA). SKY showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18 (Figure 2). The derivative chromosome 17, der(17), had positive 17pTEL and cep17 signals (Figure 3) but did not have a positive cep18 signal (Figure 4). The deriv-ative chromosome 18, der(18), had positive 18pTEL and cep18 signals (Figure 4) and a positive cep17 signal (Figure 3). The sSMC had only a positive cep18 signal (Figure 4). These findings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromo-some 18. The karyotype of the fetus was thus 47,XY, t(17;18)(q11.1;q11.2),+mar.ish der(17)t(17;18)(q11.1; q11.2)(17pTEL+, D17Z1+),der(18)t(17;18)(q11.1; Key Words:chromosome 17, chromosome 18, marker chromosome 18, prenatal diagnosis,
reciprocal translocation, small supernumerary marker chromosome
1 6 13 19 20 21 22 Y X 14 15 16 17 der(17) 18 der(18) 7 8 9 10 q11.1 11 12 2 3 4 5 q11.2 mar
Taiwan J Obstet Gynecol • June 2010 • Vol 49 • No 2 190
C.P. Chen, et al
q11.2)(18pTEL+,D18Z1+,D17Z1+),+der(18)(D18Z1+). Oligonucleotide-based aCGH demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18.
Discussion
To date, at least seven cases of sSMCs with minute cen-tric fragments of chromosome 18 have been reported [10]. Starke et al [11] and Liehr et al [12] reported the prenatal diagnosis of 47,XY,+mar de novo in all 15 col-onies of amniocytes because of advanced maternal age
and fetal cystic hygroma. The sSMC was ascertained to be min(18)(:p11.1q11.1:) with positive cep18 by cenM-FISH and subcenM-FISH, and the pregnancy was terminated. Starke et al [11] and Manvelyan et al [13] reported the diagnosis of 47,XX,+mar[23]/46, XX[17] in the peripheral blood of a 36-year-old female with primary infertility and an atrial septal defect. The sSMC was ascertained to be min(18)(:p11.21q11.1:) with positive pcp18 and cep18 by cenM-FISH and subcenM-FISH and RP11-151D11(13.08 Mb) on the sSMC. Backx et al [14] and Tönnies et al [15] reported the diagnosis of 47,XY,+mar[21]/46,XY[2] at 6 years of age and 47,XY,+mar[25]/46,XY[9] at 18 years of age in a normal healthy adolescent male whose healthy mother 1 6 13 19 20 21 22 X Y 14 15 16 17 -17 -18 -18 -17 -18 18 7 8 9 10 11 12 2 3 4 5 der(17) der(18) 17 18 mar
Figure 2.Spectral karyotyping using 24-color spectral karyotyping probes demonstrate a reciprocal translocation involving chromosomes 17 and 18, and a marker chromosome derived from chromosome 18.
Figure 3. Fluorescence in situ hybridization using a 17p-specific telomeric probe (spectrum green) and chromosome 17 centromeric probe (spectrum red) shows a red signal on chromosome 17, derivative chromosome 17 [der(17)] and der(18) but not on the marker chromosome (mar).
der(18)
der(17) mar
18
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Figure 4. Fluorescence in situ hybridization using an 18p-specific telomeric probe (spectrum green) and chromosome 18 centromeric probe (spectrum red) shows a red signal on chromosome 18, der(18) and marker chromosome mar.
Taiwan J Obstet Gynecol • June 2010 • Vol 49 • No 2 191 A Small Supernumerary Marker From Chromosome 18 also had 26% mosaicism for marker chromosome. The
sSMC was ascertained to be min(18)(:p11.21q11.1:) by cenM-FISH and subcenM-FISH with positive RP11-151D11(13.08 Mb) and a 13.99 Mb-centromere dosage gain by aCGH. Liehr [10] reported the diagnosis of 47,XX,+mar[26]/46,XX[14] in the peripheral blood of a healthy, normal 31-year-old woman. The sSMC was ascertained to be min(18)(:p11.21q11.1:) by cenM-FISH and subcenM-cenM-FISH with a breakpoint in 18p between RP11-794M8 (13.03 Mb) and RP11-411B10 (13.99 Mb) using bacterial artificial chromosomes (BACs). Baldwin et al [16] reported 47,XX,+mar (80%)/ 46,XX (20%) in an adult female who had difficulty in conceiving. The marker chromosome was also found in her normal father and normal daughter. The sSMC was ascertained to be mar(18)(:p11.21q11.1:) by subcenM-FISH, and 1 Mb in size on sSMC using BACs and aCGH. Baldwin et al [16] additionally reported the prenatal diagnosis of 47,XX,+ mar (100%) de novo by amniocentesis because of an advanced maternal age. The additional case reported by Baldwin et al was normal with no dysmorphic features or developmental delay at 4 months of age. The sSMC was ascertained to be mar(18) (:p11.21q11.1:) by subcenM-FISH, and 2.6 Mb in size on sSMC as determined by BACs and aCGH. Liehr et al [6] reported the diagnosis of 47,XX,+ mar(100%) de novo in the peripheral blood of a 1-month-old girl without visible clinical signs, except hyperbilirubinemia, an atrial septal defect and open duc-tus Botalli. The sSMC was ascertained to be min(18) (:p11.1q11.2:) by cenM-FISH and subcenM-FISH. Our case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 with-out phenotypic consequences.
Acknowledgments
This work was supported by research grants NSC-96-2314-B-195-008-MY3 and NSC-97-2314-B-195-006-MY3 from the National Science Council, and MMH-E-98004 from Mackay Memorial Hospital, Taipei, Taiwan.
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