Small Supernumerary Marker Chromosomes Research Articles

Erratum to: Familial small supernumerary marker chromosome (sSMC) (14) (:p11-q11:) in a child with translocation down syndrome

Erratum to: Familial small supernumerary marker chromosome (sSMC) (14) (:p11-q11:) in a child with translocation down syndrome

Familial small supernumerary marker chromosome (sSMC) (14)(:P11–q11:)In a child with translocation down syndrome

We report a case of familial small supernumerary marker chromosome (sSMC)in a child with translocation Down syndrome (DS)and mother. The GTG-banded chromosomal analysis of DS child revealed 47,XY,+21,+mar and mother karyotype was 47,XX,+mar. The GTG-banded sSMC had a similar morphology of small acrocentric chromosomes. Fluorescence in situ hybridization (FISH)evaluation of sSMC using centromere probes(13/21,14/22,22)confirmed sSMC as derivative chromosome 14. The sSMC was not specifically stained with whole chromosome paint and arm-specific probes for chromosome 14;thus it has been described as der(14)(:p11-q11:).The phenotypic changes were not evident, may be due to trisomy condition in the child or the sSMC contain repetitive sequences.

Small supernumerary marker chromosome originating from chromosome 10 associated with an apparently normal phenotype

Small supernumerary marker chromosomes (sSMC) originating from chromosome 10 are rare. Only seven cases have been documented, and among those three cases were diagnosed prenatally. We reported on another prenatal diagnosis of a de novo mosaic sSMC in an apparently normal female fetus whose mother had conceived with assisted reproductive technology (ART) procedures. G-banding analysis of amniotic cells was performed. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies with chromosome 10-specific alphoid satellite DNA probe were used to identify the chromosome 10 origin of the sSMC. Further FISH study with telomeric sequence probes showed that the sSMC lacked a hybridization signal, suggesting that the marker could be a ring chromosome. FISH studies using BAC clone probes specific for the regions within 10p11.2, 10q11.1, and 10q11.2 showed that the short arm breakpoint was located between 29.8 and 30.7 Mb from the 10p telomere, and that the long arm breakpoint was located less than 43.6 Mb from the 10p telomere. The karyotype of the fetus was 47,XX,+mar. ish der(10)(SKY+ CEP 10+, CTD-2130I7+, RP11-89J23-)/46,XX. Oligonucleotide microarray-based copy number variations (CNV) analysis was also performed and showed a 6.7 Mb duplication from 10p11.2 to 10q11.2 (36.2-42.9 Mb) with Affymetrix SNP-array 6.0 genotype: arr cgh. 10p11.2q11.2(CN_519687 --> CN_541524) X 3. At the 1-year follow-up, the baby did not have any findings of the trisomy 10p syndrome. This observation provided further credence to the concept that additional chromosome material of proximal 10p11.2 may not contribute to the trisomy 10p syndrome phenotype.

A small supernumerary marker chromosome present in a Turner syndrome patient not derived from X- or Y-chromosome: a case report

BackgroundSmall supernumerary marker chromosomes (sSMC) can be present in numerically abnormal karyotypes like in a 'Turner-syndrome karyotype' mos 45,X/46,X,+mar.ResultsHere we report the first case of an sSMC found in Turner syndrome karyotypes (sSMCT) derived from chromosome 14 in a Turner syndrome patient. According to cytogenetic and molecular cytogenetic characterization the karyotype was 46,X,+del(14)(q11.1). The present case is the third Turner syndrome case with an sSMCT not derived from the X- or the Y-chromosome.ConclusionMore comprehensive characterization of such sSMCT might identify them to be more frequent than only ~0.6% in Turner syndrome cases according to available data.

P15.14: Absence of ultrasound abnormalities in a fetus with a small supernumerary marker chromosome (sSMC) found at prenatal diagnosis

P15.14: Absence of ultrasound abnormalities in a fetus with a small supernumerary marker chromosome (sSMC) found at prenatal diagnosis

Analysis of the small supernumerary marker chromosome in Turner syndrome with 45, X/46, X, + mar karyotype

To identify the origin and study the morphology of small supernumerary marker chromosome (sSMC) in Turner syndrome with 45, X/46, X, + mar karyotype. Using the conventional chromosome G-banding technique, 10 cases of Turner syndrome with 45, X/46, X, + mar chromosome karyotype were obtained, dual-color fluorescence in situ hybridization was applied to study the origin and morphology of the sSMC. In the 10 cases of Turner syndrome with 45, X/46, X, + mar karyotype, the sSMC of 7 cases was derived from X chromosome [sSMC(X)], the sSMC of 2 cases was derived from Y chromosome [sSMC(Y)] and the remaining 1 case was derived from the autosome. There were 4 cases of ring(r) chromosomes and 3 of centric minutes (min) in the 7 sSMC (X) cases. In the 2 sSMC(Y), one case was dicentric (dic) and the other was centric minute (min). The sSMC originated from the autosome was a centric minute (min). The origin of sSMC of Turner syndrome with 45, X/46, X, + mar karyotype was almost all from sex chromosomes, and rarely from autosomes. sSMC can exist as isodicentric, ring, or centric minute. The molecular cytogenetic features of the sSMC can provide useful information for genetic counseling, prenatal diagnosis and treatment of the Turner syndrome patients with a 45, X/46, X, + mar karyotype.

A case of an infertile male with a small supernumerary marker chromosome negative for M-FISH and containing only heterochromatin

To describe the case of a 32-year-old infertile male with small supernumerary marker chromosome (sSMCs) in 80% of peripheral lymphocytes. G-banding, C-banding, STRP analysis, M-FISH and molecule diagnosis of Y-chromosomal microdeletions were performed to determine the origin of sSMCs. The karyotype of this patient was established as 47, XY, +mar/46, XY. C-banding showed that the marker chromosome was composed of heterochromatin without visible euchromatic material. No positive result was obtained in STRP, M-FISH and the microdeletion analysis of Y- chromosome. The small supernumerary marker chromosome could play a causative role in male infertility although the mechanism remains to be elucidated.

Handling small supernumerary marker chromosomes in prenatal diagnostics

Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be thoroughly characterized by conventional banding cytogenetics and are equal in size or smaller than chromosome 20. They are present in 0.075% of prenatal cases and, overall, approximately 3 million people worldwide are carriers of a sSMC. In prenatal cases with ultrasound abnormalities, sSMCs are found in up to approximately 0.2% of the cases. First described in 1961, it is now known that sSMCs have no phenotypic effects in approximately 70% of de novo cases. Nonetheless, in at least 30–50% of prenatally detected sSMC cases, the pregnancy is terminated; that is, for a certain percentage of potentially healthy children with a sSMC, an abortion is induced. This situation can only be improved by providing increased amounts of and more reliable information on sSMCs. This article provides an overview on current state-of-the-art technologies and how sSMC analysis can be optimized in prenatal diagnostics.

Extra marker chromosome in newborn children.

A total of 6 children with an extra, small metacentric chromosome have been found in a population study of 11,148 newborn children. No deleterious phenotypic effect was found in the carriers. The derivation and possible effect of the marker chromosomes are discussed.

Molecular cytogenetic characterization of two small supernumerary marker chromosomes derived from chromosome 19

Molecular Cytogenetic Characterization of Two Small Supernumerary Marker Chromosomes Derived from Chromosome 19 Thomas R. Dennis,* Gina N. Raptoulis, Heather J. Stalker, Debra Boles, Jeanne M. Meck, Donna M. Krasnewich, Raphael Schiffmann, and Roberto T. Zori Shodair Children’s Hospital, Department of Genetics, Helena, Montana College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, Florida Department of Pediatrics, Division of Genetics, University of Florida, Gainesville, Florida Carilion Labs, Cytogenetics Laboratory, Charlotte, North Carolina Quest Diagnostics/Nichols Institute, Cytogenetics Laboratory, Chantilly, VA Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

Characterization of a prenatally assessed de novo supernumerary minute ring chromosome 20 in a phenotypically normal male

BackgroundThe heterogeneous group of small supernumerary marker chromosomes (sSMCs) presents serious counseling problems, especially if they are present de novo and diagnosed prenatally. The incidence has been estimated at 1 in 1000 prenatal samples. We present a case of mosaic sSMC diagnosed prenatally after amniocentesis. The sSMC was characterized by various molecular cytogenetic techniques and determined to be a r(20) chromosome. After genetic counseling, the parents decided to continue the pregnancy, and a boy with minor phenotypic variants was born after 39 weeks of pregnancy. The case is compared with four other cases of prenatally detected r(20) mosaicism.ResultsHere we describe a 3 months old male child with normal pre- and postnatal development and with a de novo ring supernumerary marker chromosome in amniocytes cultures. Using new fluorescence in situ hybridization (FISH) techniques, three distinguishable sSMCs (cryptic mosaicism), all derived from chromosome 20, were observed, including ring and minute chromosomes. This heterogeneity was impossible to detect by the conventional G-banding technique or conventional FISH technique that were used before the application of new FISH techniques (subcentromere-specific multicolor-FISH [subcenM-FISH]) and a probe, specific for the 20p12.2 band. The sSMC present in 25% of the cells was present as r(20)(::p12.2~12.3->q11.1::)[5]/r(20;20)(::p12.1->q11.1::q11.1 >p12.1::)[2]/min(20;20)(:p12.1->q11.1::q11.1->p12.1:)[1]. The final karyotype was 47,XY,+r(20)[25%]/46,XY[75%].ConclusionWe emphasize the importance of application of molecular cytogenetics in a prenatally diagnostic laboratory and description of more cases to enable a better genetic counseling and risk evaluation.

Inherited Tetrasomy of the 15p-15q11.2 Region Associated with Normal Phenotypes

We analyzed the 15p-15q11.2 region of human chromosome 15 that was tetrasomic in a three-generation family with a chromosome 15-derived small supernumerary marker chromosome (der15, sSMC). This stable, inherited sSMC was present in four family members. The breakpoint that led to the formation of der15 was established by fluorescence in situ hybridization (FISH) using 18 bacterial artificial chromosomes (BACs) mapping to the pericentric region of 15q. The breakpoint was mapped to an 11 kb sequence in the 15q11.2b sub-band, and it resides in a NF1 pseudogene, within the BAC 810K23 clones. FISH mapping verified the localization of the overlapping 18 BAC clones in the 15q11.2 region, and confirmed that large duplications were spanning to 15q13.1 including the PWS/AS critical region. Carriers of the der15 pseudodicentric isochromosome are healthy, and these cases support that inherited tetrasomy of the 19.4 Mb chromosomal segment of the 15p-q11.2b region has no phenotypic consequences.

Extra small marker chromosome associated with normal phenotype due to 3:1 disjunction of t(14;22) in a parent. Implications for the origin of marker chromosomes

A family with segregation of a translocation t(14;22) (q31;q11) is is reported. The proband was ascertained by chromosome analysis after repeated spontaneous abortions in his wife. His normal sister was found to have the karyotype 47,XX,+ der (22). The small size and banding pattern of chromosome 22 make it difficult to determine the breakpoint with certainty, but it was judged to be at q11. This small marker chromosome could thus be similar to the one found in the cat eye syndrome, and further studies may cast light on gene(s) involved in this syndrome.

Partial trisomy of chromosome 22 resulting from a supernumerary marker chromosome 22 in a child with features of cat eye syndrome

Small supernumerary marker chromosomes are present in about 0.05% of the human population. In approximately 28% of persons with these markers (excluding the approximately 60% derived from one of the acrocentric chromosomes), an abnormal phenotype is observed. We report on a 3-month-old girl with intrauterine growth retardation, craniofacial features, hypotonia, partial coloboma of iris and total anomalous pulmonary venous return. Cytogenetic analysis showed the presence of a supernumerary marker chromosome, identified by fluorescence in situ hybridization as part of chromosome 22, and conferring a proximal partial trisomy 22q22.21, not encompassing the DiGeorge critical region (RP11-154H4 + , TBX1-). This observation adds new information relevant to cat eye syndrome and partial trisomy of 22q.

Thirty-two new cases with small supernumerary marker chromosomes detected in connection with fertility problems: Detailed molecular cytogenetic characterization and review of the literature

Thirty-two patients with fertility problems were identified as carriers of small supernumerary marker chromosomes (sSMC). Molecular cytogenetic techniques were used to characterize their chromosomal origin. Together with the other cases available in the literature 111 sSMC cases have now been detected in connection with fertility problems in otherwise clinically healthy persons and characterized for their genetic content. According to this study, in 60% of the cases the sSMC originated from chromosomes 14 or 15. Euchromatic imbalances were caused by the sSMC presence in 30% of the cases. Notably, in 53% of infertile sSMC carriers, the sSMC was parentally transmitted. As we found indications of an as yet unknown mechanism for the elimination of sSMC from the human gene pool, sSMC could also play a role in elucidating the process of chromosome gain and loss during evolution. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.

Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity?

BackgroundSmall supernumerary marker chromosomes (sSMC) are present ~2.6 × 106 human worldwide. sSMC are a heterogeneous group of derivative chromosomes concerning their clinical consequences as well as their chromosomal origin and shape. Besides the sSMC present in Emanuel syndrome, i.e. der(22)t(11;22)(q23;q11), only few so-called complex sSMC are reported.ResultsHere we report three new cases of unique complex sSMC. One was a de novo case with a dic(13 or 21;22) and two were maternally derived: a der(18)t(8;18) and a der(13 or 21)t(13 or 21;18). Thus, in summary, now 22 cases of unique complex sSMC are available in the literature. However, this special kind of sSMC might be under-diagnosed among sSMC-carriers.ConclusionMore comprehensive characterization of sSMC and approaches like reverse fluorescence in situ hybridization (FISH) or array based comparative genomic hybridization (array-CGH) might identify them to be more frequent than only ~0.9% among all sSMC.

Mechanisms and Consequences of Small Supernumerary Marker Chromosomes: From Barbara McClintock to Modern Genetic-Counseling Issues

Supernumerary marker chromosomes (SMCs) are common, but their molecular content and mechanism of origin are often not precisely characterized. We analyzed all centromere regions to identify the junction between the unique chromosome arm and the pericentromeric repeats. A molecular-ruler clone panel for each chromosome arm was developed and used for the design of a custom oligonucleotide array. Of 27 nonsatellited SMCs analyzed by array comparative genomic hybridization (aCGH) and/or fluorescence in situ hybridization (FISH), seven (approximately 26%) were shown to be unique sequence negative. Of the 20 unique-sequence-positive SMCs, the average unique DNA content was approximately 6.5 Mb (range 0.3-22.2 Mb) and 33 known genes (range 0-149). Of the 14 informative nonacrocentric SMCs, five (approximately 36%) contained unique DNA from both the p and q arms, whereas nine (approximately 64%) contained unique DNA from only one arm. The latter cases are consistent with ring-chromosome formation by centromere misdivision, as first described by McClintock in maize. In one case, a r(4) containing approximately 4.4 Mb of unique DNA from 4p was also present in the proband's mother. However, FISH revealed a cryptic deletion in one chromosome 4 and reduced alpha satellite in the del(4) and r(4), indicating that the mother was a balanced ring and deletion carrier. Our data, and recent reports in the literature, suggest that this "McClintock mechanism" of small-ring formation might be the predominant mechanism of origin. Comprehensive analysis of SMCs by aCGH and FISH can distinguish unique-negative from unique-positive cases, determine the precise gene content, and provide information on mechanism of origin, inheritance, and recurrence risk.

Small supernumerary marker chromosomes (sSMC) in humans; are there B chromosomes hidden among them

BackgroundSmall supernumerary marker chromosomes (sSMC) and B-chromosomes represent a heterogeneous collection of chromosomes added to the typical karyotype, and which are both small in size. They may consist of heterochromatic and/or euchromatic material. Also a predominance of maternal transmission was reported for both groups. Even though sSMC and B-chromosomes show some similarity it is still an open question if B-chromosomes are present among the heterogeneous group of sSMC. According to current theories, sSMC would need drive, drift or beneficial effects to increase in frequency in order to become B chromosome. However, up to now no B-chromosomes were described in human.ResultsHere we provide first evidence and discuss, that among sSMC B-chromosomes might be hidden. We present two potential candidates which may already be, or may in future evolve into B chromosomes in human: (i) sSMC cases where the marker is stainable only by DNA derived from itself; and (ii) acrocentric-derived inverted duplication sSMC without associated clinical phenotype. Here we report on the second sSMC stainable exclusively by its own DNA and show that for acrocentric derived sSMC 3.9× more are familial cases than reported for other sSMC.ConclusionThe majority of sSMC are not to be considered as B-chromosomes. Nonetheless, a minority of sSMC show similarities to B-chromosomes. Further studies are necessary to come to final conclusions for that problem.

Chromosomal Abnormalities in Saudi Children of Jeddah City

It is attempted to estimate the incidence of chromosomal disorders, constitutional karyotype and cytogenetic patterns of chromosomal abnormalities in the Western Saudi region. Further, associations between socio-demographic, obstetrical, medical and environmental factors were also attempted. Overall incidence of chromosomal disorders was estimated at 2.8 and 2.4 for Down syndrome per thousand Saudi live births. Cytogenetic analysis revealed preponderance of numerical (92%) aberrations than structural (8%). Down syndrome was the most frequent form of the chromosomal disorders; in addition, trisomies of chromosome 13 and 18 and monosomy of X was found in lesser frequencies. A rare form of chromosomal configuration with translocation of chromosome 7 and 10, extra marker chromosome and pericentric inversion in chromosome 3 were also observed. Trisomy 21 was recorded to have high frequency (94%); other forms like Robertsonian translocation and mosaicism were also detected in lesser frequency. A significant association between advanced mother ages was confirmed, other factors have no bearing. Findings are: The estimated incidence of overall chromosomal disorders is lower, but incidence of Down syndrome is higher compared to national and international frequencies. Down syndrome is the most frequently encountered disorder and karyotypic techniques effectively help diagnosing in most of the cases.

A new small supernumerary marker chromosome, generating mosaic pure trisomy 16q11.1–q12.1 in a healthy man

Here we report on a healthy and fertile 30 years old man, who was carrier of a small supernumerary marker chromosome (sSMC). The application of molecular techniques such as fluorescence in situ hybridisation (FISH), microdissection and reverse painting, helped to characterize the sSMC which resulted to be derived from chromosome 16. In fact, the presence of euchromatin material from the long arm (16q) in the sSMC was demonstrated, and the karyotype can be written as mos 47, XY,+min(16)(:p11.1->q12.1:)[20]/46, XY [10].