Rare case of mosaicism for chromosome 18, karyotype: 46, XX, del(18) (p11)/46, XX, i(18q)

Rare mosaicism of chromosome No 18 is described. The proposita is 5.5 years old and has two cell clones: 50% of cells are monosomic for 18p and 50% have isochromosome i18q. The ratio of these clones (1:1) is found to be similar at the age of the proposita 2.5 and 5.5 years. The proposita has some phenotypic characters of both 18p- (ptosis, epicanthus, deformed carious teeth, falled back sternum etc.) and trisomy 18q (contraction of external auditory meatus, femur luxatus congenitus etc.) syndromes. A possible mechanism for the origin of such a mosaicism is discussed.     

Pericentric inversions of the X chromosome. A new observation and review of the published cases

A pericentric inversion of the X chromosome-inv(X) (p11.3q22) is transmitted in 3 generations. Male and female carriers are normal. The proposita is tetraplegic, severely retarded and suffers from general seizures. Grand mal seizures are known in the mother and grandmother. Different proportions of inactive X chromosomes in the proposita and the normal sister are discussed. The published cases of inv(X) are reviewed.     

rDNA and acrocentric chromosomes in man

Summary A malformed female infant was found to have a 46,XX complement with a chromosome 8 shorter than normal with a secondary constriction and satellites on the short arm. Chromosome studies on the clinically normal father showed a balanced translocation between chromosome 8 and 13, i.e., 46,XY,t(8;13) (p21 p12). The proposita, carrier of the unbalanced form of the translocation, resulted partially monosomic for short arm of chromosome 8 (8p-) and partially trisomic for short arm of chromosome 13.The levels of DNA complementary to rRNA (normal in the father who had 10 NOR and increased in the proposita who had 11 NOR) confirmed our interpretation of the rearrangement.     

Transmission of a t(13q22q) chromosome observed in three generations with segregation of the translocation D1-trisomy syndrome.

A case of an inherited type of D/G translocation D1-trisomy syndrome was described. A female proposita who had the clinical signs of D1-trisomy syndrome was found to have a chromosome complement of 46,XX,--G,+t(DqGq). examination of Q- and G-stained karyotypes revealed that the chromosomes involved in the translocation were members of Nos. 13 and 22, or t(13q22q) with breaks at p12 of both chromosomes. C-stained figures also showed a large heterochromatin block in its centromeric region. The t(13q22q) chromosome was transmitted from the paternal grandmother of the proposita through at least three generations.     

Coumarin induced acral skin necrosis associated with hereditary protein C deficiency

Hemorrhagic skin necrosis of the toes was observed in a patient with heterozygous protein C deficiency (protein C:Ag 32% and protein C activity 30%) on the 4th day of coumarin treatment overlapping with effective intravenous anticoagulation with heparin. Family studies revealed protein C deficiency in two sisters of the proposita without a history of thromboembolic disease. Immunologic studies in the proposita at the time of coumarin necrosis revealed slight depression of complement factor C4 and the presence of immune complexes. The present case and review of the literature show that the pathogenetic mechanism leading to coumarin necrosis in patients with protein C deficiency seems not yet to be fully understood.     

Familial translocation 22/Y and partial autosomal trisomy in a young girl

Report on a translocation t(22;Y)(q12;p 13) with conservation of the NOR in normal members from 2 generations of a family. The proposita has in addition a small autosomal duplication, probably (1)(q44-ter) which could explain her mental deficiency.     

46,XX,-12,+der(12),rcp(3;12)(p25.1;p13.31)pat karyotype in a girl. Probable subregional assignment of glyceraldehyde-3-phosphate dehydrogenase locus to 12p13.1----p13.31 by exclusion mapping

A female infant with partial trisomy 3p and a terminal deletion 12p, due to a paternal (3;12)(p25.1;p13.31) translocation is described. Normal glyceraldehyde-3-phosphate (GAPD) activity in the proposita tentatively excludes GAPD locus from the deleted segment. Therefore, the region for this locus is reduced to 12p13.1----p13.31.     

Type C brachydactyly transmitted through four generations

We report a type C brachydactyly transmitted through four generations, with incomplete penetrance and feet abnormalities in the proposita.     

A de novo 3p13 deletion induced by a complex chromosomal rearrangement combined with a pericentric inversion of chromosome,inv(3)(p13q12), and a translocation between chromosome 3 and 8, t(3;8)(q13.1;q24.2), in a child with developmental delay

A de novo complex chromosomal rearrangement is very rare but likely to be present in a child with developmental disabilities and physical alterations. A child presented in this study showed global developmental delay and some typical phenotypes. Initial karyotyping and FISH analysis in the patient showed an apparently de novo balanced translocation between chromosome 3 and 8, t(3;8)(q13.1;q24.2). Further analysis using multiplex ligation-dependent probe amplification and array-based comparative genomic hybridization revealed a cryptic microdeletion on 3p13 region. Nearly one-third of balanced rearrangements are reported to involve cryptic disruptions at breakpoints, however, the microdeletion of the proposita was present in non-translocated region of the chromosome 3. After careful reevaluation of the results, a pericentric inversion, inv(3)(p13q13.1) that induced deletion was revealed. The clinical features of developmental delay in cognition, language, and motor function and facial and physical phenotype of the proposita were similar to those found in the children with 3p13 deletion. This case shows that combined molecular cytogenetic techniques with routine karyotyping are very useful to identify subtle genomic changes associated with abnormal phenotypes.     

Partial trisomy for the distal part of the short arm of chromosome 11 due to paternal translocations 11/5]

A girl with partial trisomy for the short arm of chromosome 11 resulting from an unbalanced translocation 46,XX,der 5, t(5,11) (p 15,p14) pat is described. The clinical findings are compared with those of other patients with partial trisomy 11p. The translocation in the balanced form was present in the fater, the brother, and the grandmother of the proposita.     

Centric fission of chromosome No. 7 in three generations

Summary Centric fission of chromosome no. 7 (cen fiss 7) was found after G-, Q-, and C-banding of blood lymphocyte chromosomes in the healthy female proposita, referred for chromosome analysis because of three previous abortions. The same abnormality was found in a further five family members (three females, two males) and had been transmitted over three generations.     

Familial t(X;2) (p223;q323) with partial trisomy 2q and male and female balanced carriers

Summary A familial t(X;2) (p223;q323) is responsible for partial trisomy 2q in the proposita, a 3-year-old girl with severe mental retardation and hypotrophia. It is present in the balanced state in the mother, two daughters, and one son. X-replication was studied after BUDR incorporation and acridine organge staining. The reproductive impairment of balanced X/autosome translocations is discussed.     

Familial D/E translocation

Summary A familial D/E translocation is described. The proposita, a girl with features of the trisomy-E₁ syndrome, had 47 chromosomes. The extra chromosome was a small acrocentric one. Her mother and little brother had 46 chromosomes, and showed a missing chromosome in the groups D and E, and an extra chromosome in the groups C and G. The former had a subterminal centromere. The latter could not be dinstinguished morphologically from the other small acrocentrics.The morphology and the autoradiographic analysis of the chromosomes concerned in the translocation, indicated that it was a (17q+; 14q-) translocation. It could also be proved that the extra chromosome of the proposita represented mainly a partial trisomy 14. The father and little sister of the patient had a normal karyotype.A comparison of the karyotypes, found in the children of the present family and in cases of D/E-translocation reported in the literature, pointed to a high frequency of non-disjunction in D/E-translocation carriers. As a possible explanation, a convergent orientation of a trivalent at metaphase I of meiosis is proposed.     

Partial trisomy of the long arm of chromosome 2 by malsegregation of a maternal translocation t(2;7)(q321;p22)

A patient with partial trisomy 2q due to the malsegregation of a balanced maternal (2;7) translocation is reported. The proposita, who died a few hours after birth, presented the characteristic clinical features: microcephaly, prominent forehead, hypertelorism, depressed nasal bridge, upturned nostrils. Her karyotype was 46,XX,der(7),t(2;7)(q321;p22) mat.     

Deletion of the long arm of chromosome 8 resulting from a de novo translocation t(4;8) (q13;q213)

Summary Report is given of a mentally retarded and dysmorphic patient with a partial monosomy 8q, resulting from a de novo translocation t(4;8)(q13; q213).Determination of erythrocyte gluthathione reductase (E-GSR) activity in the proposita shows activity in the normal range. Previous evidence for of the assignment of E-GSR locus to the short arm of chromosome 8 is confirmed.     

Cytogenetical and clinical investigations in aplastic anaemia (Fanconi's type)

Summary Cytogenetic investigations were performed in a 10 year-old girl with clinical features of Fanconi's anaemia, i.e.: growth retardation, skin pigmentation, bilateral absence of thumbs, anaemia, leukopenia, etc. A variety of structural anomalies as chromatid gaps and exchanges, chromatid and isochromatid breaks were observed. The same type of chromosome anomalies was found in the parents and in the younger sister of the proposita, the older sister being karyotypically normal.Dermatoglyphic investigations revealed in the proposita the absence of t triradius on both palms and an increased mean ridge count, increased also in all the family members. Genetic implications and possible mechanisms of chromosomal aberrations are discussed.This investigation was supported by a grant from C.N.R., Italy.Professor of Child Health.     

Triosephosphate isomerase deficiency with hemolytic anemia and severe neuromuscular disease. Familial and biochemical studies of a case found in Spain

Summary A 16-month-old girl of Spanish origin with chronic hemolytic anemia and severe neuromuscular disease was found to have markedly reduced triosephosphate isomerase (TPI) activity in her erythrocytes, leukocytes, and platelets. Both parents and some other family members had moderately reduced erythrocyte TPI activity in accordance with the autosomal recessive mode of inheritance in this enzymopathy. Latex ingestion and latex-stimulated histochemical NBT reduction by the patient's granulocytes were normal.Zymosan-stimulated superoxide radical ( ) formation, not previously studied in TPI-deficient granulocytes, was also within normal limits. Starchgel electrophoresis of TPI in both erythrocytes and leukocytes of the proposita and her parents was normal. Molecular studies of deficient TPI showed a normal kinetic pattern with markedly reduced heat instability.Immunologic studies demonstrated no cross reacting material in proposita leukocytes and a normal molecular specific activity. These studies suggest that molecular instability might cause both enzymatic and antigenic degradation of the TPI molecule and, therefore, TPI deficiency in our patient.     

Partial trisomy for the distal part of the long arm of chromosome 15 due to a balanced maternal X/15 tranlsocation]

Partial trisomy for the distal part of 15q due to a balanced maternal translocation t(X;15) is described in a 21-month old girl with growth and psychomotor retardation and a cranio-facial dysmorphism ressembling that of a previously reported patient. Treatment of lymphocytes with BrdU has shown inactivation of the normal X in the mother, and inactivation of either the abnormal or the normal X in the proposita. When the abnormal X was inactivated, the extent of inactivation of the autosome was variable.     

Ataxic gait and mental retardation with absence of the paternal chromosome 8 and an idic(8)(p23.3): imprinting effect or nullisomy for distal 8p genes?

A female child with mild dysmorphisms, motor and mental retardation had a 45,XX,-8,-8,+psu dic(8)(p23.3) karyotype in blood lymphocytes, skin fibroblasts and in a lymphoblastoid cell line. DNA analysis showed that the proposita was nullisomic for the 8pter region distal to D8S264, at less than 1 cM from the telomere. Analysis of DNA polymorphisms of 38 loci spread along the entire chromosome 8 revealed that only maternal alleles were present, distributed in four heterozygous and four homozygous regions. This finding indicated that the rearrangement occurred during maternal meiosis in a chromosome recombinant with a minimum of seven crossovers. To our knowledge this is the first case of uniparental maternal disomy for chromosome 8 and of nullisomy for the distal 1-cM portion of the short arm. The available data are in favour of the assumption that no imprinted genes are present on chromosome 8. Thus, dysmorphisms, motor and mental retardation of the proposita are likely to be caused by the nullisomy for the region distal to D8S264, a region in which a recessive gene for epilepsy with progressive mental retardation is known to be located. Received: 16 December 1996 / Revised: 24 January 1997