Normal superoxide dismutase-1 (SOD-1) activity with deletion of chromosome band 21q21 supports localization of SOD-1 locus to 21q22

Summary The gene for superoxide dismutase-1 (SOD-1) is clearly on chromosome 21, although there is disagreement on the precise band location of SOD-1 on the long (q) arm of number 21. We report a patient with normal superoxide dismutase-1 (SOD-1) activity and an interstitial deletion of chromosome 21 resulting in monosomy for band q21. His phenotype is characterized by moderate mental retardation, a long narrow face, high and arched palate, cardiac murmur, undescended testes, and long hyperflexible extremities. The normal SOD-1 activity supports localization of this enzyme to 21q22.1.     

Ring chromosome 21 transmitted from mother to daughter: its stability in a lymphoblastoid cell line

A female infant with a high-pitched cry and hypertelorism but an otherwise normal facies was found to have the karyotype 46,XX,r(21)(p11.2q22.3). The r(21) was transmitted from the phenotypically normal mother. In both cases, the structure and behavior of the r(21) were rather stable in peripheral lymphocyte cultures. This stable nature of the r(21) was also confirmed in a lymphoblastoid cell line derived from the proband, where the normal-sized r(21) was persistent in most cells in prolonged culture for at least 5 months.     

Inherited ring chromosome 8 without loss of subtelomeric sequences

We report the first case of inherited ring chromosome 8 syndrome without loss of subtelomeric sequences. The proband is a 6 1/2-year-old boy with short stature, microcephaly, mild mental retardation, and behavioral problems including hyperactivity and attention deficit. His mother presented the same physical features but intelligence was normal. Family history also revealed an uncle and a grandmother, with short stature and microcephaly. Moderate mental retardation was reported in the uncle. Karyotypes and fluorescence in situ hybridization (FISH) analyses were performed on peripheral blood lymphocytes for both child and mother. The child's karyotype was reported as 46,XY,r(8)(p23q24.3)[24]/45,XY,-8[2] and the mother's karyotype 46,XX,r(8)(p23q24.3)[22]/45,XX,-8[2]/47,XX,r(8)(p23q24.3), +r(8)(p23q24.3)[1]. FISH studies showed no deletion of subtelomeric sequences for both child and mother indicating that no or little chromosomal euchromatic material has been deleted. These findings indicate that ring chromosome 8 without loss of subtelomeric sequences can be inherited and that carriers in a same family present with cognitive function ranging from mild mental retardation to normal intelligence.     

A case of 21q-syndrome with half normal SOD-1 activity

A male Japanese infant was found to have a chromosomal aberration of del(21)(qter leads to q22.1-2) and decreased superoxide dismutase (SOD) activity in erythrocytes and polymorphonuclear and mononuclear leukocytes. The cuprozinc enzyme (SOD-1) level was 40-50% of normal, while the cyanide-insensitive manganese enzyme (SOD-2) activity was within the normal range. Determination of SOD activity in blood cells is a valuable method of classification of the syndrome.     

Dosage effects for superoxide dismutase-1 in nucleated cells aneuploid for chromosome 21.

Assays of the activity of chromosome 21 determined superoxide dismutase-1 (SOD-1) in lymphocytes and polymorphonuclear granulocytes have demonstrated 38% and 40% increases, respectively, in cells from individuals with trisomy 21. Similarly, SOD-1 activity in trisomic fibroblasts is increased by 81%, while cells monosomic for chromosome 21 have only 60% of normal activity. Taken together with the data on SOD-1 activities in trisomic erythrocytes and platelets, the present results firmly confirm the existence of a true dosage effect for this enzyme in cells aneuploid for chromosome 21. However, the results of assays of the activity of glutathione peroxidase in trisomic fibroblasts did not confirm the possibility previously reported of a chromosome 21 related dosage effect for this enzyme.     

A case of 21q-syndrome with normal SOD-1 activity

Summary A female infant with del(21)(pterq22.1-2:) constitution identified by G, Q, and R banding is reported. She had marked mental and physical retardation, generalized hypertonia, microphthalmia with persistent hypoplastic primary vitreous, blepharochalasia, high nasal bridge, micrognathia, malformed ears with preauricular pits, and overlying fingers. The assay for superoxide dismutase-1 (SOD-1) activity in the patient revealed a normal value and it was suggested that the gene locus for SOD-1 in 21q22.2qter is not compatible with the presence of the gene dosage effect in the monosomic state.     

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.     

A familial extra small marker autosome in persons with normal phenotype

The propositus was referred because of sterility and oligospermia. His karyotype was 45, XY, t(13q14q). His father was dead; his mother and the only brother, who was fertile, both had 47 chromosomes, but a normal phenotype and normal intelligence. The additional chromosome was three quarters the size of a G chromosome and had satellites on the short and long arms.     

Maternal transmission of ring chromosome 21

Summary A psychomotor-retarded infant with minor dysmorphic signs and a karyotype 46.XY,r(21)mat in lymphocytes is reported. The mother is phenotypically normal but shows the same unstable r(21). This is another case demonstrating that a chromosomal aberration does not necessarily lead to infertility by meiotic failure. Nevertheless, segregation of ring chromosomes is problematic for two reasons: mitotic problems of the ring structure itself and synaptic difficulties during the pachytene stage.     

Ring 13 in an adult male with a 13:13 translocation mother

A male with a ring 13 chromosome [r(13)(p11q34)], mild mental retardation, short stature, oligoasthenospermia, and few dysmorphisms is reported. His mother who had a poor reproductive history is carrier of a t(13q13q), featuring a dicentric NOR-negative element. The clinical significance of the r(13) and the mother's unusual karyotype are discussed.     

Sotos syndrome with a balanced reciprocal translocation t(2;12)(q33.3;q15)

A balanced reciprocal translocation, 46,XY, t(2;12), was detected in a male infant who had the characteristic features of Sotos syndrome. His father's karyotype was normal, but his mother and an older brother had the same chromosomal abnormality without a history or clinical features of Sotos syndrome.     

Xp22.3; Yq11.2 chromosome translocation and its clinical manifestations

We report clinical and molecular investigations in a boy with karyotype 46,Y,der(X)t(X;Y)(qter-->p22.3::q11.21-->qter) and his mother with karyotype 46,X,der(X)t(X;Y)(qter-->p22.3::q11.21-->qter). Haplo-insufficiency for the Xp22.3-->pter chromosomal region in the boy resulted in postnatal growth retardation, developmental delay, partial ichthyosis and facial dysmorphism, but normal external genitals. His mother has a normal phenotype with normal stature and gonadal function but borderline intelligence. FISH-analysis showed a duplication of the Y-heterochromatin probe in the proband and a deletion of the Y933D4 probe in his mother. Molecular investigations situated the Xp22.3 breakpoint between DXS278 and the KAL gene and the Yq11.21 breakpoint between the DYS391 and DYS390 in the proband and his mother. X-inactivation study was performed by analysis of the polymorphic CAG-repeat in the androgen-receptor gene as described showing a normal random (40% versus 60%) inactivation pattern in the mother. The manifestations in male and female with loss of the Xp22.3-->pter and gain of the Yq11.21-->qter chromosomal region are discussed.     

Inherited pericentric inversion of Y-chromosome with trisomy 21. A case report

A 13-year-old boy with clinical features of Down syndrome was investigated. His karyotype was 47,X,inv(Y),+21. The proband's father and two elder brothers were also found to have the inv(Y). A spontaneous chromatid break was observed in the long arm of the X chromosome[? fra (X)] in 2% of the cells. The mother had two spontaneous abortions. This is the first case of trisomy-21 with inv(Y) in our population. This finding might be fortuitous. The frequency of inv(Y) in Down syndrome is not known.     

Paternal trisomy 21 mosaicism and Down's anomaly

Summary A family is described in which the 1-year-old boy had clinical Down's syndrome with regular trisomy 21 in the karyotype. The mother was healthy, was aged 22 years at the birth of her son, and had a normal 46,XX karyotype. The father (23) was phenotypically also normal, but proved to be a mosaic for trisomy 21. Four of the 60 of his cells examined contained the 47,XY,21+ chromosome set.Since only a small proportion of cultured lymphocytes is usually trisomic in such mosaics, many similar cases could be overlooked in routine examinations.

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Zusammenfassung Es wird eine Familie beschrieben, in welcher ein einjähriger Junge ein Down-Syndrom mit regulärer Trisomie 21 aufwies. Die gesunde Mutter, 22 Jahre alt bei der Geburt des Kindes, zeigte einen normalen 46,XX-Karyotyp. Der Vater, 23 Jahre alt, war ebenfalls phänotypisch normal; er wies jedoch ein Mosaik für Trisomie 21 auf. 4 von 60 untersuchten lymphocyten-Mitosen zeigten den Karyotyp 47,XY, 21+.Da bei derartigen Mosaiken meist nur ein kleiner Anteil kultivierter Lymphocyten die Trisomie aufweist, dürften viele ähnliche Fälle bei Routineuntersuchungen übersehen werden.

     

Partial trisomy of chromosome 21 by maternal translocation t(15;21) (q26.2; q21)]

A balanced reciprocal translocation, t(15;21) (q262;q21) was observed in the mother and maternal grandfather of two patients. The propositus, who received the abnormal chromosome 15 from his mother, is trisomic for the distal part of chromosome 21, and his phenotype is that of classical trisomy 21. His sister, who is trisomic for the proximal part of 21q, is slightly retarded but developmentally normal otherwise.     

Transmission of ring chromosome 18 46,XX/46,XX,r(18) mosaicism in a mother and ring chromosome 18 syndrome in her son.

Inheritance of ring chromosomes is reported infrequently. The authors report on a phenotypically and mentally normal mother with ring chromosome 18 mosaic with a normal cell line and her polymalformed son with non-mosaic 46,XY,r(18) karyotype.     

H-Y antigen expression in a case of XX true hermaphroditism

Summary Cells from an XX true hermaphrodite expressed a reduced amount of H-Y antigen when compared with normal XY cells and with cells from his father, who had an XY/XX chromosomal constitution. His mother had a normal karyotype and was H-Y negative. The four brothers of the patient were clinically and karyotypically normal. An X-Y interchange followed by random inactivation of the X chromosome is proposed to explain the H-Y antigen titer found in the patient.     

Dosage effect of the cytoplasmic superoxide dismutase (SOD-1) gene in the erythrocytes of Down's syndrome patients]

The activity of cytoplasmic superoxydase (SOD-1) was studied in erthrocytes of 17 patients affected with Down's syndrome (trisomy 21) and in 26 healthy persons. A 1.56-fold increase of the enzyme activity was observed in the group of patients as compared with the control group. This could be explained as the dosage effect of the corresponding gene located in the chromosome 21.     

'The effect of micronutrients on superoxide dismutase in senescent fibroblasts'

The specific activities of zinc/copper (Zn/Cu)-superoxide dismutase (SOD-1) and manganese (Mn)-superoxide dismutase (SOD-2) were assayed in young passage 5 fibroblasts and in serially subcultured cells that were characterized as senescent at passages 15-35. SOD-1 and SOD-2 activities did not significantly change in senescent and young cells cultured in either routine medium [minimum essential medium 1 (MEM1)], or in Zn, Cu and Mn supplemented medium (MEM2) containing normal human plasma levels of the cations. SOD-1 and SOD-2 activities, however, underwent parallel progressive significant activity increases in senescent passage 20 and 25 cells, which peaked in value in passage 30 and 35 cells subcultured in supplemented medium (MEM3) containing triple human plasma levels of the cations. Concurrently, superoxide radical generation rates underwent progressive significant increases in senescent passage 15-25 cells, which peaked in value in passage 30 and 35 cells subcultured in MEM1 or MEM2. These rates, however, were significantly lowered in senescent cells subcultured in MEM3. We infer that it was only possible to significantly stimulate SOD-1 and SOD-2 activities in senescent MEM3 cultured cells enabling them to combat oxidative stress.     

Inheritance of a translocation between chromosomes 12 and 16 in a family with recurrent miscarriages and a newborn with Down syndrome carrying the same translocation

Reciprocal translocation carriers have reduced fertility, increased risk of spontaneous abortion or unbalanced karyotype in their offspring. Here, we report the inheritance of a translocation between chromosomes 12 and 16 in a family with recurrent miscarriages and a newborn with Down syndrome carrying the same translocation. Chromosomal analysis from fetal amniotic fluid and peripheral blood lymphocytes from the family were performed at the Cukurova university hospital in Turkey. We assessed a family in which the translocation between chromosomes 12 and 16 segregates; one of the eight progenies with the karyotype 47,XY,+21,t(12;16)(q24;q24) was heterozygote for the translocation and presented with Down syndrome. His mother is phenotypically normal, one brother and one sister were also carrying the same translocation. Apparently, this rearrangement occurred due to the unbalanced chromosome segregation of the mother [t(12;16)(q24;q24)mat]. This case will enable us to explain the behavior of segregation patterns and the mechanism for each type oftranslocation from carrier to carrier and their effects on reproduction and numerical aberrations. The t(12;16) is also associated with fetal wastage and may play a role in the etiology of the family's miscarriages. These findings can be used in clinical genetics and may be used as an effective tool for reproductive guidance and genetic counseling.