A case of r(21) with stigmata of atypical Down syndrome

Summary A case of r(21) with stigmata of atypical Down syndrome is presented. Karyotype of the proposita was determined as 45,XX,-21/46,XX,-21, +r(21)/47,XX,-21,+r(21),+(21). Most ring chromosomes showed double-sized ring chromosomes, which were trisomic for 21p11-21q22.3 and monosomic for 21q22.3-qter. SOD-1 activity revealed only slight elevation. The mechanism of ring formation is discussed.     

Molecular evidence for true isochromosome 21q

Summary In one family a duplicated 21q was shown to be a true isochromosome, which segregates from mosaic mother to non-mosaic child with full Down syndrome phenotype. Densitometric analysis of Southern blots, using probe pPW228C for the distal long arm of chromosome 21, indicated that the 21q duplication contains two copies of the allele detected by the probe. Maternal mosaic karyotype of 45,XX,-21/46,XX/46, XX,-21,+21i(21q) also suggested transverse mitotic centromere division as the origin of the 21q isochromosomes. Morphologic analysis of chromosome heteromorphisms strengthened this interpretation because the free 21 missing in the cell line with 45 chromosomes was also missing in cells with the isochromosome. In a second family the cytogenetic data also suggested transmission of an i(21q) from mosaic mother to nonmosaic Down syndrome child but molecular evidence did not prove identity of alleles in the duplicated chromosome 21.     

Structural chromosome abnormalities in Down syndrome: a study of two families.

Two families were ascertained through a proband with Down syndrome and a structural rearrangement involving two chromosomes 21. It is suggested that in one patient the chromosome is an isochromosome formed by misdivision of the centromere of a maternal telocentric chromosome 21 and that in the other a Robertsonian translocation involving chromosome 21 was inherited from the mother, who is a 46,XX/46,XX, -21,+t(21q21q) mosaic. The origin of the mosaicism is discussed and considered to be likely to be the result of breakage and reunion at the chromatid, rather than the chromosome, level.     

Unstable telocentric chromosome produced after centric misdivision of a 21q/21q translocated element

Summary An unstable telocentric chromosome was found in an individual with Down's syndrome and an unusual chromosomal mosaic, 46,XX, t(21q21q)+,21-/46,XX,21p-/45,XX,21-. As the 21q/21q chromosome was of paternal origin, based on the characteristics of its centromeric heterochromatin and on the characteristics of both 21 chromosomes of the father, it was concluded that its formation involved centric breakage and loss of centromeric material. The cell line with the 21p- chromosome may have originated from the translocation by an asymmetric misdivision of the reduced centromeric material. Of the two telocentrics produced by this fracture, one, possessing the smaller amount of centromeric apparatus, would be immediately lost; the other would be retained, but complete activity of its centromere would not be restored. It would therefore be unstable and might be lost.     

A child with a 21-ring chromosome, 45,XX,21-/46,XX,21r investigated with the banding technique

Summary Chromosomal analysis of lymphocytes and fibroblasts in a slightly retarded 7-month-old female infant with some minor malformations showed a mosaicism 45,XX,G-/46,XX,Gr. The ring chromosome was identified as No. 21 by banding technique.

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Zusammenfassung Chromosomenuntersuchungen an Lymphocyten und Fibroblasten bei einem 7 Monate alten Mädchen mit leichter statomotorischer Entwicklungsverzögerung und degenerativen Stigmata zeigten ein Mosaik 45,XX,G-/46,XX,Gr. Durch die Bandentechnik mit Trypsinbehandlung konnte das Ringchromosom als Nr.21 identifiziert werden.

     

Reciprocal translocations and full trisomy (trisomy 18 and trisomy 21) in the offspring

In this report, we present examples of trisomy 18 and trisomy 21, both resulting from maternal reciprocal translocations: 46, XX, t(5;18) (q21;q11) and 46, XX, t(5;21) (p11.2;p11), respectively.     

Cell-cycle kinetics of cell lines from patients with chromosomal mosaicism

Lymphocyte cultures from five patients with chromosomal mosaicism (two 47,XY,+21/46,XY, one 47,XX,+21/46,XX, one 45,X/46,XX, and one 47,XXY/46,XY) were studied using sister chromatid differential staining technique for cell kinetic evaluation. Aneuploid and normal cell lines were compared to identify changes in cellular proliferation in vitro that could be related to cellular selective advantage and cell-line-proportion changes occurring with age. Comparison of the percentage of cells in different cell generations in 48, 72, and 96 h-cultures shows no differences between the aneuploid and normal cell lines indicating that cell-cycle kinetics is similar in these cells in vitro.     

16种罕见的人类染色体异常核型报告

通过对患有闭经、自发流产、死胎、死产等患者外周血淋巴细胞染色体检查,发现16种新的罕见人类染色体异常核型,它们是46,XY,t(6;11)(q25;p15);46,XY,inv(3)(p25;q29);46,XY,t(7;18)(q10;p10);46,X,t(X;13)(q24;q14);46,XY,t(4;7)(q33;q22);46,XY,t(8;15)(q24;q15);46,XY,t(2;17)(q33;q25);46,XX,t(4;7)(q34;q11);46,XX,t(1;3)(p36;p23);46,XX,t(4;6)(q35;p11);46,X,inv(X)(q22;q28);46,XX,t(7;10)(p11;q26);46,XX,t(3;6)(p21;q23);46,XX,t(8;16)(p21;p13);46,XX,t(8;9)(q21;q34);46,XY,t(17;22)(q21;q11)。描述了患者的临床表现,并对生殖异常患者染色体畸变与其表型效应关系进行探讨。Abstract：By examining the lymphocytic chromosomes of peripheral blood from patients with amenorrhea,spontaneous abortion and stillbirth history, .the 16 rare species of human chromosomal abnormal karyotypes were discovered. They wre 46,XY,t(6;11)(q25;p15);46,XY,inv(3)(p25;q29);46,XY,t(7;18)(q10;p10);46,X,t(X;13)(q24;q14);46,XY,t(4;7)(q33;q22);46,XY,t(8;15)(q24;q15);46,XY,t(2;17)(q33;q25);46,XX,t(4;7)(q34;q11);46,XX,t(1;3)(p36;p23);46,XX,t(4;6)(q35;p11);46,X,inv(X)(q22;q28);46,XX,t(7;10)(p11;q26);46,XX,t(3;6)(p21;q23);46,XX,t(8;16)(p21;p13);46,XX,t(8;9)(q21;q34);46,XY,t(17;22)(q21;q11). Their clinical situation were described. Discussion on the relationship between the chromosomal aberrations and phenotype effect indicates the importance of chromosome karyotyping in patients with abnormal reproductive history.     

Partial monosomy 8p and partial trisomy 8p with moderate mental retardation.

A female patient with mosaicism for partial monosomy 8p and partial trisomy 8p is presented. Her karyotype is 46,XX, del(8)(p21)/46,XX, dup(8)(p21----pter). She showed minimal dysmorphic features, agenesis of the corpus callosum and moderate developmental delay. There is no previous report of mosaicism for partial monosomy and partial trisomy 8p. The clinical findings in the presently described patient are less severe than those reported in cases with only monosomy or trisomy of the distal part of chromosome 8.     

Karyological characteristics of Down's syndrome: clinical and theoretical aspects

These data have been collected from St. Petersburg Down Syndrome Register that comprises information on 1778 liveborn children with the Down syndrome, including three twin sets, ascertained within 1970-1996. Karyotypes were obtained in 1223 cases, of which 1119 (90.7%) displayed regular trisomy. Mosaicism was found in 44 cases (3.6%), including 21 males and 24 females, and among these one familial case of mosaicism in a daughter and in a healthy mother. Of 70 cases of translocations, 41(5.7%) were Robertsonian D ones. 21 (17 inherited, 16 de novo and 8 of unknown origin), 28 translocations of isochromosomes 21q; 21q (1 inherited translocation 21; 22, 22 de novo and 5 of unknown origin). One child received the anomaly from his 46XX/45XX, t(D;G) mother-carrier. In 6 cases, free trisomy 21 was associated with structural or numerical anomalies: 46XY,t(13;14)mat + 21 in twins, 47XY,t(C;C) + 21, 47XY,t(10;15)pat + 21, 47XY,inv(19)mat + 21, 47XX + 21/48XX + 21 + ring, 48XXX + 21. In 12 families parental mosaicism was shown or suspected. In 6 families one parent had chromosome anomaly, in three cases it was not inherited: t(15;22) and t(6;21) in mothers and an additional small marker in a father. In cases confirmed cytogenetically an increased sex ratio was shown (679 males and 551 females, SR = 1.23), but it was not shown in patients not tested cytogenetically (264 males and 275 females, SR = 0.96, different from the expected 297 males and 242 females, P < 0.01).     

Offspring of patients with Down syndrome

An incident of birth of a child in 16-year-old patient with typical phenotype of Down's syndrome is described. The karyotype of the proband is 47, XX + 21, while that of the child is 46, XX. Analysis of the literature data and the author's observations showed that the total ratio of trisomics and non-trisomics in the offspring of women with Down's syndrome is 9:18, which considerably differs from theoretically expected and suggests that selection against anomalous gametes exists.     

Trisomy 21 by mirror duplication 46,XX,psu dic(21)ter rea (21q21q) (author's transl)

"Mirror image" duplication of chromosome 21 -- 46,XX,pter dic(21)ter rea(21q21q) -- was observed in a patient with the complete phenotype of trisomy 21 and a ses-sesquialtère de la SOD1.     

Pericentric inversions of chromosome number 9: benign or harmful?

Pericentric inversions of chromosome number 9 have been studied in 4 different probands: a normal female with designation 46,XX,inv(9)(p12q13); a male with Down syndrome designated as 47,XY,+21,inv(9))p13q13); a premature infant with multiple, congenital malformations who was 46,XX,inv(9)(p12q21), and a Down syndrome proband with 47,XYqs,+21,inv(9)(p13q21). All 4 cases were shown to be inherited based on family studies. These families are discussed with reference to the literature as to what possible effect this structural change could have on the reproductive capability of a normal carrier and what guidelines are available for counseling such a carrier.     

Partial monosomy of the long arm of chromosome 16 in a malformed newborn: Karyotype 46,XX,del(16)(q21)

Summary A polymalformed newborn with partial monosomy for the long arm of chromosome 16 is presented. Karyotype 46,XX,del(16)(q21).     

Double autosomal aberration: trisomy 21 and familial reciprocal translocation t(10;12)(p14;q21)]

A child with the Down syndrome revealed besides a regular trisomy 21, an enlargment of the short arm of chromosome 10, and the deletion of the long arm of chromosome 12. The proband's mother, who was phenothypically normal woman, appeared to be a carrier of the reciprocal translocation, her karyotype being: 46, XX, rep (10;12) (10qter leads to leads to 10p14; 12q21 leads to 12qter; 12pter leads to 12q21 : 10p14 leads to 10pter). Hence, the proband had double chromosomal aberration 47, XX, +21, rcp (10; 12) (10qter leads to 10p14 : 12q21 leads to leads to 12qter; 12pter leads to 12q21 : 10p14 leads to 10pter) mat. There is no reason to relate hard manifistation of the Down syndrome with the detected translocation. The influence of the mathernal non-devision in the meiosis and the rise of the trisomy 21 is discussed. In the following pregnancies it is advisable to amniocentesis.     

Prenatal diagnosis of mosaicism identified in amniotic fluid cell cultures

Chromosomal mosaicism in prenatal diagnosis is an important problem to be solved immediately and the probable phenotypic reflections should be explained to the family. We report two numerical and two structural mosaicisms detected in amniocyte cultures. The first fetus had a 47,XY,+mar[10]/46,XY[10] karyotype. The marker chromosome was shown to be derived from chromosome 15 by FISH method. The newborn had intrauterine growth retardation and cerebral thrombosis and died at the 29th day of age. The second fetus had a 45,X[4]/46,XX[26] karyotype. The parents refused cordocentesis and decided to terminate pregnancy in the 21st week. The third case, presented with bilateral large choroid plexus cysts, had a 46,XX, dup(1)(q22-q32)[9]/46,XX[21] karyotype. The parents' karyotypes were normal and the pregnancy was aborted in the 23rd week of gestation. The second structural abnormality was reported as 46,XX,t(6;11)(q23; p13)[3]/46,XX[20]. The mosaicism was detected in only one flask. The parents decided to continue pregnancy and cordocentesis could not be performed due to the fetal and placental position. The baby was born at term. Peripheral blood lymphocyte culture resulted in a 46,XX normal karyotype. Information and risks were explained to all families during genetic counseling. Mosaicism in prenatal diagnosis needs both detailed examination and follow up, since clinical findings depend on the type of abnormality.     

Trisomy 7p due to a mosaic normal/dir dup(7)(p13----p22). Syndrome delineation, critical segment assignment, and a comment on duplications

A 4 4/12 year-old girl with a peculiar phenotype due to a 46,XX/46,XX, dir dup(7)(p1300----p2200) karyotype is described. The comparison with about ten similar cases permitted a better delineation of the 7p trisomy syndrome and the assignment of the band 7p21 as the critical one. Mechanisms for the origin of homogeneous and mosaic duplications, including one model based on a meiotic half chromatid duplication, are discussed.     

新生儿缺氧性脑病伴46,XX,-21,+t(21;21)罕见核型一例

Abstract:This report describes a cytogenetic aberration in one neonatal patient with hypoxic-ischemic encephalopathy.A rare karyotype,46,XX,-21,+t(21;21), was detected.This de nono chromosomal abnormality may be caused by the meiotic non-disjunction of chromosomes during gametogenesis along with the formation of Robertsonian translocation between homologous chromosome 21.     

A clinical and cytogenetic investigation carried out in a special institution for mentally retarded patients: preliminary results concerning 82 cases of oligophrenia (author's transl)]

A clinical and cytogenetic investigation carried out in a special institution for mentally retarded patients revealed 82 cases of oligophrenia, amongst whom were found 56 normal karyotypes (68.3%). Out of 25 karyotypes with chromosome anomalies or variants there were 18 cases of trisomy 21 and 7 others: one case of mosaicism with balanced translocation, 46,XX/46,XX,6p+,17q-; one case of partial trisomy, 46,XX,11q+; one case of pericentric inversion, 46,XY,inv(1) (p13,q21); one case with 8% chromosome breaks; three cases of marker chromosomes, of which one was of karyotype 46,XX,1qh+, and two (oligophrenic sisters) 46,XX,21p+. Moreover, there was an interesting case of testicular feminisation in a 9-year-old girl with karyotype 46,XY. The authors' results corroborate those obtained in several important previous studies based on much larger numbers of patients. Amongst the 56 cases where the karyotype was shown to be normal, there were 15 for whom a probably exogenic cause of the oligophrenia could be established, occurring mainly during the perinatal period. The authors were also able to confirm that the genetic factor plays an important role in the incidence of mental retardation, since in 22 examined patients, i.e. 26.8% of all cases, the condition was of familial type. Some interesting observations of idiopathic oligophrenia are reported, as well as several cases with well-known syndromes (Crouzon's and Cornelia de Lange's syndromes, hypothyroidism). Two cases of incest between father and daughter, which had produced children with serious oligophrenia associated, in one case, with deaf-mutism, microphthalmia, microcephaly and sclerocornea, are also discussed. The data show that mental retardation can frequently have a genetic cause, either of mendelian, chromosomal or multifactorial origin.     

Maternally transmitted extra ring(21) chromosome in a boy with Down's syndrome

Summary An 11-month-old boy with typical Down's syndrome is presented. His karyotype was 47,XY,+r(21); the erythrocyte superoxide dismutase-1 (SOD-1) activity was elevated. His phenotypically normal mother showed 46,XX,r(21) karyotype and normal SOD-1 activity. Analysis of chromosomal heteromorphism revealed that in addition to the ring, a normal chromosome 21 was transmitted from the mother.