Small supernumerary marker chromosomes (sSMCs) have been described from all human chromosomes with different sizes and shapes. However, it is difficult to know the clinical manifestations associated with them, because such knowledge depends on the size, presence of euchromatic material, degree of mosaicism and/or uniparental disomy (UPD)

Bizzoco, Domenico

Cignini, Pietro

Gabrielli, Ivan

Giorlandino, Claudio

Mesoraca, Alvaro

PubMed

Small supernumerary marker chromosomes (sSMCs)

have been described from all human chromosomes

with different sizes and shapes. However, it is difficult

to know the clinical manifestations associated with

them, because such knowledge depends on the size,

presence of euchromatic material, degree of mosaicism

and/or uniparental disomy (UPD).

A case report of a familial small supernumerary marker

chromosome (sSMC) through a structural and a segregation

study is reported.

Case repor

Bizzocco, Domenico

Scientific Open-access Literature Archive and Repository

Journal of Prenatal Medicine 2007; 1 (3): 41-44 41Ivan Gabrielli1Domenico Bizzoco1Alvaro Mesoraca1Pietro Cignini2Claudio Giorlandino21“ARTEMISIA” Fetal-Maternal Medical Centre, Department of Genetics and Molecular Biology, Rome, Italy2“ARTEMISIA” Fetal-Maternal Medical Centre, Department Prenatal Diagnosis, Rome, ItalyReprint requests to: Ivan Gabrielli, MD“ARTEMISIA” Fetal-Maternal Medical Centre, Department of Molecular Genetic Viale Liegi, 45 - 00198 Rome - ItalyTel.: +39068505806E-mail: ivan.gabrielli@artemisia.itSummarySmall supernumerary marker chromosomes (sSMCs)have been described from all human chromosomeswith different sizes and shapes. However, it is difficultto know the clinical manifestations associated withthem, because such knowledge depends on the size,presence of euchromatic material, degree of mosaicismand/or uniparental disomy (UPD).A case report of a familial small supernumerary markerchromosome (sSMC) through a structural and a segre-gation study is reported.Case reportA particular class of observable trisomies in the study ofthe human karyotype is constituted from the presence ofsmall supernumerary marker chromosomes (sSMCs)(1). sSMC are structurally abnormal chromosomes thatcannot be identified or characterized unambiguously byconventional banding cytogenetics alone, and are (ingeneral) equal in size or smaller than a chromosome 20of the same metaphase spread.Generally the marker chromosomes respond to threedifferent structural typologies: those that have a uniquecentromere (monocentric), those that have two cen-tromeres (dicentric) and those without centromere(acentric) (2) e analyzed the case of a man whose kary-otype results to be 48,XY,+2mar (Fig. 1), condition foundfollowing the analysis of follow-up on a foetus with kary-otype 47,XX,+mar (Fig. 2) to such purpose we tried tocharacterize at structural level and to define the mecha-nism of segregation in at least three generations by Flu-orescent In Situ Hybridization (FISH) (3). When a chro-mosomal abnormality after foetal karyotyping is ob-served, the analysis of the karyotype of the family com-ponents is mandatory to understand if the presence ofthe sSMCs is to be consider “de novo” mutation or trans-mitted through the germinal line.Until today a lot of methods were used to characterizethe nature of sSMCs in different kind of tissues. Weanalysed with classical cytogenetics method karyotypesof the individuals of three generations (fatherly grand-mother, father, mother and foetus) with the purpose todefine a scheme of distribution of the sSMCs.A FISH analysis was made on the available sample: am-niotic fluid (foetus), seminal liquid (father), peripheralblood (father, mother and fatherly grandmother) pre-pared as described by standard protocols (4). The hy-bridization has been effected with Hybrite as describedby factory protocols (Vysis). In our case it was not been possible to characterize thesSMC by the usual GTG banding because of its smalldimensions.The results of the study of the karyotypes obtained byperipheral blood of the parents of the foetus and on thefatherly grandmother brought the followings results (Fig.1):– maternal karyotype: 46,XX– fatherly karyotype: 48,XY,+2mar– karyotype fatherly grandmother: 47,XX,+mar.The FISH analysis has been used for characterizing themolecular nature of the marker.In our case positiveness of hybridization was for theprobe LSI D15S11 SpectrumOrange-CEP15 Spec-trumGreen Vysis in all samples. In such hybridizationboth centromeric probes and euchromatic subcen-tromeric probes were seen. In all the analyzed sam-ples, excluded that fatherly, a trisomy of the centromer-ic region has been found (Fig. 2; FISH on foetal kary-otype), while in the FISH analysis on fatherly blood atetrasomy of such region (Fig. 2; FISH on father’s kary-otype) has been found. A double positivity for hy-bridization was found for the subcentromeric region,for all the analyzed samples. To understand as thechromosome marker, derivative of the chromosome15, could have segregated during the spermatogene-sis, two different analyses have been performed usingFISH on nucleuses interfasic on fatherly sperms. Thefirst one using probes centromeric CEP15 Spectrum-Green Vysis and CEP12 SpectrumOrange Vysis (Fig.3; first image). From the picked data he can clearly de-duce a condition of apparent mosaicism for the chro-mosome 15 with the 61% of monosomy, the 37% of di-somy and him 1% of trisomy (Tab. I). The second hy-A case report of a meiotic segregation study on a small supernumerary marker chromosomeA CASE REPORT_Gabrielli  3-01-2008  14:48  Pagina 41I. Gabrielli et al.42 Journal of Prenatal Medicine 2007; 1 (3): 41-44Figure 1Foetal KaryotypeFather’s KaryotypeA CASE REPORT_Gabrielli  3-01-2008  14:48  Pagina 42A case report of a meiotic segregation study on a small supernumerary marker chromosomeJournal of Prenatal Medicine 2007; 1 (3): 41-44 43Figure 2Father’s Karyotype with FISH for CEP15 and DAPI counterstainingFoetal Karyotype with FISH for CEP15 and DAPI counterstainingA CASE REPORT_Gabrielli  3-01-2008  14:48  Pagina 43bridization has been effected using the probe LSID15S11 used for the other tissue analyzed in prece-dence (Fig. 3; second image).The results mostly showan exhaustive vision of as is distributed the positivityfor hybridization on the analyzed nucleuses.In fact in-side the monosomic population is observed a 44% ofcontaining nucleuses the whole chromosome 15, whilethe remainder 17% is constituted by nucleuses withthe only marker. Therefore it can be inferred that therelationship between the segregation of the chromo-some marker against the chromosome 15 is of around1:4 (Tab. II). In the disomic population (initially es-teemed to 37%) was observed a 23,5% of nucleusescontaining a whole chromosome 15 and an SSMC(15q10+/15q11-13+/15q10+/15q11-13-); while 10,4%were nucleuses with two SSMCs (15q10+/15q11-13-);the remainder 3,2% consists instead of two wholechromosomes 15 (15q10+/15q11-13+). Finally in thetrisomic population, however found in low frequency, amixed population of nucleuses was found with twowhole chromosomes 15 and an SSMC and vice versa(0,5% each). Considering all these data we deduced that the total de-gree of segregation will results from the sum of the dif-ferent percentage of segregation related to the differentpopulations: 17% + 23,5% + 10,4% + 0,5% + 0,5% =52%.Among the nucleuses where the SSMC is present a de-gree monosomy vs. disomy of 1:4 (10,4% + 0,5% and17% + 23,5% + 0,5% respectively) has been found.DiscussionConsidering the data from classical cytogenetics studiesmade on peripheral blood of different individuals, itwould be attend for a high degree of disomy in the sper-matic cells of the individual 48,XY,+2mar. Therefore thefurther observations of molecular cytogenetics have al-lowed us to observe a prevalence of monosomic sper-matic cells (61%) and a lower degree of disomic cells(37%). This mosaicism is presumably explainable with astrong instability of the pairing complex of the four SSM-Cs during the meiotic prophase. Besides such observa-tions there are no data for establishing if there are even-tually potential evolutionary pressures during the vari-ous stages of the male gametogenesis.References1. Liehr T, Mrasek K, Weise A, Dufke A, Rodríguez L,Martínez Guardia N, Sanchís A, Vermeesch JR, Ramel C,Polityko A, Haas OA, Anderson J, Claussen U, vonEggeling F, Starke H. Small supernumerary marker chro-mosomes--progress towards a genotype-phenotype corre-lation. Cytogenet Genome Res 2006;112(1-2):23-34.2. Liehr T, Claussen U, Starke H. Small supernumerary mark-er chromosomes (sSMC) in humans. Cytogenet GenomeRes 2004;107:55-673. Crolla JA. FISH and molecular studies of autosomal super-numerary marker chromosomes excluding those derivedfrom chromosome 15: II. Review of the literature. Am JMed Genet 1998;75:367-3814. Rooney D.E. & Czepulkowski B.H.. Human Cytogenetics apratical approach 1986; IRL Press.I. Gabrielli et al.44 Journal of Prenatal Medicine 2007; 1 (3): 41-44Table I Crom. 12 Crom. 15Monosomy 3920/4000 2456/400098% 61%Nullisomy 0 5/40001%Disomy 800/4000 1493/40002% 37%Trisomy 0 50/40001%Table II15q10 15q11-130 spots 1 spots 2 spots 3 spots1 spot 260/1530 680/1530 0 0(17%) (44.5%)2 spots 160/1530 360/1530 50/1530 0(10.5%) (23.5%) (3.2%)3 spots 0 7/1530 7/1530 0(0.5%) (0.5%)Figure 3A CASE REPORT_Gabrielli  3-01-2008  14:48  Pagina 44

A case report of a meiotic segregation study

on a small supernumerary marker chromosome

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A case report of a meiotic segregation study on a small supernumerary marker chromosome

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