fra(1) (p11), fra(1) (q22) and r(1) (p11q22) in a retarded girl.

A mentally retarded girl with a 46,XX/47, XX+r(1) (p11q22q22p11)/47, XX+r(1) (p11q22) fra(1) (p31) fra(1) (p11) fra(1) (q22) karyotype who inherited the fragile sites from the normal mother was studied. The conicidence of fra(1) (p11) and fra(1) (q22) with the ring chromosome breakpoints strongly suggests a cause-effect relationship. This finding agrees with other reported associations between fragile sites and structural chromosome abnormalities and constitutes the fourth reported of a de novo structurally abnormal chromosome as a consequence of presumed in vivo fragile sites instability. Although risk figures for chromosome anomalies and cancer associated with fragile sites are lacking, carriers of fra (1) (p11) may have a higher risk for abnormalities of chromosome 1 in somatic and gonadal cells than the general population.     

Deletion 1q42.3----qter in a girl with psychomotoric retardation and multiple dysmorphisms

A de novo deletion 1q42.3----qter in a 10-month-old girl with psychomotoric retardation and multiple dysmorphic signs is reported. The patient's symptoms are in accordance with a recently described distal 1q deletion syndrome.     

19q distal trisomy due to a de novo (19;22)(q13.2;p11) translocation

A 2 4/12-year-old girl whith a de novo 46,XX,-22 + der(22), t(19;22)(q13.2;p11) karyotype is described. From this and other eight similar cases previously published, a typical phenotype in distal 19q trisomy is concluded.     

4p- syndrome in a girl with translocation t(1;4)(q11;p16)mat

Summary A newborn girl had features of the 4p- syndrome. Cytogenetic studies of the mother showed a translocation t(1;4)(q11;p16). The proband had the translocation, but the band 4p16 had been lost.     

De novo balanced translocation (2;10)(q24;q22) associated with mental retardation

We report a case of a reciprocal translocation between the long arms of the 2 and 10 chromosomes observed in a 14-year-old male with mild mental impairment, compulsive and obsessive behavior. The apparently balanced translocation was characterized by fluorescence in situ hybridization and the karyotype was 46, XY, t(2;10)(q24;q22). The way by balanced chromosomal translocations can lead to a disease phenotype are reviewed and discussed.     

Post-mortem studies on two patients with 1-2 band cytogenetic deletions: 10q26----qter and r(9)(p24q34)

Two severely retarded males with unbalanced karyotypes Case 1--(45,XY,--10,--15, + der(10)t,(10; 15) (q26; q13) and Case 2--46,XY,r(9) (p24q34) died at the ages of 24 and 38 years respectively. At post-mortem, a post-ductal coarctation of the aorta and a lump kidney were found in the first case. Brain pathology was normal in the first case and apart from a smaller size, was structurally normal in the second case.     

del(X)(p22.1)/r(X)(p22.1q28) Dynamic mosaicism in a Turner syndrome patient

We report on a 16-year-old patient with Turner syndrome who presented a mos 46,X,del(X)(p22.1)[35]/45,X [19]/46,X,r(X)(p22.1q28)[6]GTG-band karyotype. The R-banding showed that the abnormal X-chromosome was inactive in all 61 cells analyzed. Fluorescence in situ hybridization with a Xp/Yp subtelomeric probe revealed that both abnormal chromosomes lacked the complementary sequences, a fact consistent with a terminal deletion. Besides, the molecular analysis of the human androgen receptor gene showed that the rearranged chromosome was paternal in origin. Since the deleted and the ring chromosomes had the same size and banding pattern, and because the former was the predominant cell line, it was inferred that the Xp- formed a ring in some cells apparently without further loss of genetic material. However, the reverse sequence and even a simultaneous origin due to a complex intrachromosomal exchange are also conceivable. The mild Turner syndrome phenotype is explained by the mosaicism and by the size of the deleted segment.     

Familial unbalanced translocation t(8;15)(p23.3;q11) with uniparental disomy in Angelman syndrome

A 29-year-old male with Angelman syndrome and an unbalanced reciprocal translocation, 45,XY,-8,-15,+der(8),t(8;15)(p23.3;q11)pat, was evaluated with DNA studies. These showed the underlying mechanism to be paternal uniparental disomy. This is the second case reported of Angelman syndrome that has resulted from a familial unbalanced reciprocal translocation.     

Familial inv(1)(p3500q21.3) associated with azoospermia

Summary An inv(1)(p3500q21.3) was found in an azoospermic man, his mother and two other maternal relatives. Although the mechanisms involved are still unclear, it is stressed that pericentric inversions of chromosome 1 in which the inverted chromosome becomes submetacentric (centromeric index 0.324) apparently impair spermatogenesis.     

Balanced familial translocation t(5;19)(q12;p or q11) with phenotypical abnormalities in a girl.

Human diploid fibroblasts cultured in Dulbecco's Modified Eagle's medium (DME) were exposed to different concentrations of 15 antibiotics to determine the limiting toxic concentration. The number of cells surviving after antibiotic treatment was given as the index of toxicity. No visible chromosomal damage could be detected when half the maximal toxic concentration was applied. The maximum limiting concentration was found to be the same for both the preconfluent and postconfluent phases.     

Translocation (X;13)(p11.21;q12.3) in a girl with incontinentia pigmenti and bilateral retinoblastoma

A de novo t(X;13)(p11.21;q12.3) translocation is described in an 19-month-old girl with incontinentia pigmenti (IP) and bilateral retinoblastoma. Based on previously reported two girls and this patient, each with a structural X chromosome abnormality and IP, it was assumed that the locus for IP is at Xp11.21. Q-banding analysis revealed that the translocated chromosomes were of paternal origin. The derivative X chromosome was late-replicating in 9% of cultured peripheral blood lymphocytes and in 1% of skin fibroblasts. The erythrocyte esterase D activity in the patient was normal. Several possibilities were considered for possible causative relationship between the X/13 translocation and the development of retinoblastoma. One possibility involved functional monosomy of 13q14 in a minority of retinoblasts due to the spreading of inactivation of the translocated X chromosome segment.     

Trisomy 9p in a girl whose mother has a translocation t(9;20)(q12;p13)

Summary R banding of the fine structure of the chromatids has enabled us to study a new case of trisomy for the short arm of chromosome 9. The syndrome+9p was due to nondisjunction of a maternal translocation t(9;20)(q12;p13).     

A new case of dup(1)(q21.2q12) in an individual with mild mental retardation

Proximal duplications of the long arm of chromosome 1 are rare and the few patients that have been described in literature have multiple congenital abnormalities and/or mental retardation. The present paper describes the clinical and cytogenetic findings of an adult patient with only mild mental retardation and some minor malformations. The patient carries an inverted duplication of 1q12q21.2.     

Co-segregation of trichorhinophalangeal syndrome with a t(8;13)(q23.3;q21.31) familial translocation that appears to increase TRPS1 gene expression

Trichorhinophalangeal syndrome type I (TRPS I) is a rare autosomal dominant syndrome caused by haploinsufficiency of TRPS1 due to point mutations or deletions. Here, we report the first familial TRPS I due to a t(8;13)(q23.3;q21.31) translocation breakpoint <100 kb from the 5′ end of TRPS1. Based on the additional abnormalities observed exclusively in the index patient that are mainly compatible with clinical features of TRPS, her phenotype was defined as expanded TRPS I including brain malformations and intellectual disability. Initial analyses did not reveal any genetic defect affecting TRPS1 or any genomic alteration within the breakpoint regions or elsewhere in the genome. The pathogenic chromosome 8q23.3 breakpoint is at position g.116,768,309_116,768,310 within a transposon type I element, 87 kb from the TRPS1 5′ end. The 13q21.31 breakpoint is within a tandem repeat region at position g.65,101,509_65,101,510 (genome assembly GRCh37/hg19). This breakpoint is flanked by protocadherin 9 (PCDH9) and protocadherin 20 (PCDH20). As an outcome of the translocation, an evolutionarily conserved non-coding VISTA enhancer element from 13q21.31 is placed within the TRPS1 5′ region, 1,294 bp from the breakpoint. The increased expression of TRPS1 found by three independent methods is most probably translocation allele derived and driven by the translocated enhancer element. The index patient’s expanded phenotype presumably involves the epithelial-to-mesenchymal transition pathway that may be due to TRPS1 overexpression. Together, these findings support that the reported translocation-associated phenotypes are “cis-ruption” and TRPS1 overexpression related, the latter most probably caused by the novel enhancer element in the TRPS1 5′ region.     

Constitutional mosaic t(2;7)(q33;p22) and other rearrangements in a girl with Wilms' tumor

A 2-year-old girl with sporadic unilateral Wilms' tumor (WT) not associated with aniridia was found to have, besides other chromosome abnormalities, a t(2;7)(q33;p22) in 6% of her lymphocytes. A comparison with 7 previous WT cases without aniridia in whom diverse chromosomal aberrations were present, reveals a wide heterogeneity and lead us to tentatively classify such changes as causal, secondary, and casual.     

Paracentric inversion in a female with multiple miscarriages (7inv)(q2.13;q3.13)

Summary A phenotypically normal woman with a history of multiple miscarriages was found to have a paracentric inversion in the long arm of chromosome, which may be the reason for the miscarriages.     

Complex translocation t(9;21)(9;22)(q12p13)(q12q11) in the family of a child with 9p trisomy syndrome

Summary Leukocyte peroxidase activity was estimated in 5 patients with the juvenile form of neuronal ceroid lipofuscinosis (Spielmeyer-Vogt's disease) and in 15 healthy controls. In contradiction to recent reports normal activity of p-phenylene diamine mediated peroxidase was found in the patients. The possible role of contamination of the white cell preparation with hemoglobin is discussed.     

The eukaryotic cofactor for the human immunodeficiency virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12–p13: three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2

The eukaryotic initiation factor 5A (eIF-5A) has been identified as an essential cofactor for the HIV-1 trans-activator protein Rev. Rev plays a key role in the complex regulation of HIV-1 gene expression and thereby in the generation of infectious virus particles. Expression of eIF-5A is vital for Rev function, and inhibition of this interaction leads to a block of the viral replication cycle. In humans, four different eIF-5A genes have been identified. One codes for the eIF-5A protein and the other three are pseudogenes. Using a panel of somatic rodent—human cell hybrids in combination with fluorescence in situ hybridization analysis, we show that the four genes map to threedifferent chromosomes. The coding eIF-5A gene (EIF5A) maps to 17p12–p13, and the three pseudogenes EIF5AP1, EIF5AP2, and EIF5AP3 map to 10q23.3, 17q25, and 19q13.2, respectively. This is the first localization report for a eukaryotic cofactor for a regulatory HIV-1 protein.     

Preferential inactivation of a dupX(q23 --> q27-28) chromosome in a girl with mental retardation and dysmorphy

We report on an 18-year-old female with de novo tandem duplication Xq23-->Xq27-28. The breakpoints of the duplication segment have been mapped by FISH using a panel of locus specific YACs. Despite selective inactivation of the aberrant X chromosome, proven by a combination of molecular and cytogenetic studies, the patient exhibits mental retardation, dysmorphic features and short stature. Possible mechanisms explaining this unexpected finding are discussed.