A de novo t (X;8)(p11.2;q24.3) demonstrating Cornelia de Lange syndrome phenotype

Cornelia de Lange syndrome is a rare syndrome of hitherto unknown etiology. We present a 9-months old female patient with de novo t (X;8) (p11.2;q24.3) and Cornelia de Lange Syndrome phenotype. De novo t (X;8)(p11.2;q24.3) was not reported so far in Cornelia de Lange syndrome.     

Partial trisomy 3q in a child with sacrococcygeal teratoma and Cornelia de Lange syndrome phenotype

Partial duplication of 3q is a rare chromosomal disorder that leads to multiple congenital abnormalities such as growth retardation, microcephaly and characteristic facial features. Although the phenotype of the patient has similarities with Cornelia de Lange Syndrome they are etiologically different. We report here a 9 months old baby boy with partial duplication of 3q and features similar with Cornelia De Lange syndrome. Conventional cytogenetic analysis revealed a derivative chromosome 21. In order to determine the origin of this chromosome region we used subtelomeric FISH technique. Based on the results of all these cytogenetic studies and the physical examinations, the diagnosis is partial 3q duplication.     

Chromosome banding study of the Cornelia de Lange syndrome

Summary Chromosome studies were performed on 13 patients with the Cornelia de Lange syndrome. With the technique of chromosome banding analysis, no chromosomal abnormalities were found.     

Partial trisomy 3q

Summary A new case of partial trisomy 3q is reported in a 5-year-old female with severe congenital malformations and psychomotor retardation. A review of the literature, with a total of 11 patients, allows us to conclude that the clinical picture reminiscent of the Cornelia de Lange syndrome is caused by the trisomic state.     

De Lange Syndrome: Report of 20 Cases

Typus Degenerativus Amstelodamensis or Amsterdam dwarfism, a syndrome of unknown etiology characterized by mental retardation, a distinctive face, characteristic hands and feet, defective growth and other minor malformations, was first described by Cornelia de Lange in 1933. Approximately 69 cases, including nine autopsies, have been reported in the literature. In this paper we present a further 20, with illustrations of the syndrome from infancy to puberty (including de Lange''s original three cases). The historical, physical, laboratory and radiographic findings of de Lange''s three patients and our 20 are tabulated. Autopsy findings in one of our patients are reported and the literature is briefly reviewed.Although some observers have recently reported chromosome abnormalities in de Lange''s syndrome, we feel that the diagnosis is made from the history and physical examination and that there are no definitive laboratory aids which can confirm the diagnosis. Chromosome studies in all 20 of our patients were normal and the genetic implications are discussed.     

131例原发性闭经女性的细胞遗传学分析(含世界首报异常核型3例)

原发性闭经是一种原因复杂的疾病, 染色体异常则是发病的主要原因。通过对131例原发性闭经患者的外周血淋巴细胞染色体的G带核型分析, 发现其中83例为正常女性核型, 占63.36%; 各种异常核型48例,占36.64%, 其中包括3例世界首次报道的异常核型[46,X,t(X;1)(q22;p34); 46,X,t(X;5;6)(p11.2;q35;q16); 46,XX,t(4; 9)(q21;p22),t(6;10)(p25;q25),t(11;14)(q23;q32)]。另外, 将33例Turner’s综合征患者的主要异常体征及核型分布分别与Elsheikh等的报道进行比较, 发现矮身材、蹼颈、后发迹低和肘外翻的发生率与文献资料存在显著差异, 说明东西方Turner’s综合征患者临床体征的表现可能存在差异。通过对2例X-常染色体易位携带者的分析, 认为Xp11.2和Xq22区域可能与原发性闭经有关。     

The Self-Education of the Medical Student and Physician

A euploid/aberrant double stem line mosaicism was found in two cases of the de Lange syndrome with severe abnormalities. In both cases the structural heterozygosity of the aberrant stem line involved, apparently, the loss of chromosomal material from a smaller autosome of Group (6-12) X, probably No. 11. Differences in the cultural characteristics of de Lange cells suggest that the aberrant stem line may not proliferate in culture, so that mosaicism may not be detected. Moreover, the mosaicism may not be present in all tissues, resulting in normal cytogenetic findings as noted in a third case studied. Our findings suggest that the de Lange syndrome is the phenotypic expression of chromosomal mosaicism.     

Mice lacking sister chromatid cohesion protein PDS5B exhibit developmental abnormalities reminiscent of Cornelia de Lange syndrome

PDS5B is a sister chromatid cohesion protein that is crucial for faithful segregation of duplicated chromosomes in lower organisms. Mutations in cohesion proteins are associated with the developmental disorder Cornelia de Lange syndrome (CdLS) in humans. To delineate the physiological roles of PDS5B in mammals, we generated mice lacking PDS5B (APRIN). Pds5B-deficient mice died shortly after birth. They exhibited multiple congenital anomalies, including heart defects, cleft palate, fusion of the ribs, short limbs, distal colon aganglionosis, abnormal migration and axonal projections of sympathetic neurons, and germ cell depletion, many of which are similar to abnormalities found in humans with CdLS. Unexpectedly, we found no cohesion defects in Pds5B(-/-) cells and detected high PDS5B expression in post-mitotic neurons in the brain. These results, along with the developmental anomalies of Pds5B(-/-) mice, the presence of a DNA-binding domain in PDS5B in vertebrates and its nucleolar localization, suggest that PDS5B and the cohesin complex have important functions beyond their role in chromosomal dynamics.     

Chromosomal sensitivity to X-rays in lymphocytes from patients with Turner syndrome

Lymphocytes from patients with Turner syndrome were irradiated with X-rays (200 rad) to determine the chromosomal aberration frequency in first-division metaphases. Five patients with 45,X karyotype; three 45,X/46,Xi(X)q mosaics; one 45,X/47,XXX mosaic and 9 female controls were studied. Patients with a 45,X karyotype exhibited a radioinduced chromosomal aberration frequency similar to controls (38.6 +/- 6.37 and 36.2 +/- 5.11 respectively; p = 0.42). In the mosaics, 45,X cells had a mean frequency of 38.75 +/- 2.16; 46,Xi(X)q cells a mean of 38 +/- 2.16 and the control group a rate of 36.25 +/- 4.32. No differences were observed between 45,X and 46,Xi(X)q cells (p = 0.50), 45,X and normal cells (p = 0.24) or 46,Xi(X)q and normal cells (p = 0.35). Apparently neither the X monosomy nor the Xq isochromosome influences the 'in vitro' X-ray-induced chromosomal damage in Turner syndrome lymphocytes.     

An interstitial deletion of 8q23.3–q24.22 associated with Langer–Giedion syndrome,Cornelia de Lange syndrome and epilepsy

We present a 19-year-old male with laxity of skin and joints, sparse scalp hair, facial dysmorphism, epilepsy, multiple exostoses, scoliosis, gastroesophageal reflux, cardiovascular defects, and an 8q23.3–q24.22 deletion detected by array comparative genomic hybridization. The patient was previously misdiagnosed as having Ehlers–Danlos syndrome. However, his clinical findings are in fact correlated with trichorhinophalangeal syndrome type II/Langer–Giedion syndrome and Cornelia de Lange syndrome-4. We discuss the genotype–phenotype correlation and the consequence of haploinsufficiency of TRPS1, RAD21, EXT1 and KCNQ3 in this case.     

Translocation (13q21q). Four generation family study with analysis of satellite associations, fluorescent markers, and prenatal diagnosis.

A (13q21q) translocation was found in an infant with Down's syndrome. The 17-year-old mother and the grandmother carried the translocation 45,XX,t(13;21)(p12;q11). The great grandparents had normal karyotypes. Fluorescence marker studies suggested that the translocation originated in the great grandmother. The hypothesis was supported by satellite association studies which showed a significant excess of 13-21 and 13-15 associations in the great grandmother.     

Incidence of major chromosome aberrations in 12,319 newborn infants in Tokyo

Summary In order to ascertain the frequency of chromosome aberrations among newborn infants in Japan, a chromosome survey of a large number of newborn infants is in progress. A consecutive series of 12,319 newborn babies, 6382 male and 5937 female, have been screened for clinical manifestations of autosomal aberrations and for sex chromatin and sex chromosome aberrations. Chromosome studies were carried out on 694 infants with suspected chromosome aberrations. The clinically abnormal infants were screened by conventional staining, and banding techniques have been used in the part of the study performed since 1974. Of the clincally abnormal infants, 25 had abnormal karyotypes, including two males with a 47,XXY complement, one female with a 45,X complement, three male infants with a 47,XYY complement, two with trisomy 13 syndrome, three with trisomy 18 (including one case of mosaicism), eleven with Down's syndrome (including one case of mosaicism), one with B5p partial trisomy, one with cri-du-chat syndrome, and one with Y/D translocation. The overall results are comparable to those of previous population cytogenetic studies only in the autosomal trisomies and sex chromosome abnormalities and in that the observed frequencies were comparable to those found in studies in Caucasians.To whom offprint requests should be sent     

Translocation (13q21q)

Summary A (13q21q) translocation was found in an infant with Down's syndrome. The 17-year-old mother and the grandmother carried the translocation 45,XX,t(13;21)(p12;q11). The great grandparents had normal karyotypes. Fluorescence marker studies suggested that the translocation originated in the great grandmother. The hypothesis was supported by satellite association studies which showed a significant excess of 13–21 and 13–15 associations in the great grandmother.     

Cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia

This paper presents the results of a cytogenetic analysis in 139 Tunisian patients with de novo acute myeloid leukemia (AML), including 27 children aged 1-15 years and 112 adults. Mean age was 32 (range 1-75) and the M/F ratio was 1.43. Of our patients, 45% had apparently normal karyotypes. Acquired chromosome aberrations were found in 77 (55% ) patients. t(8;21) was identified in 27 patients (19%); t(15;17) in 13 patients (9%); deletion 7q or monosomy 7 in seven patients (5%); +8 in seven patients (5%); abnormal 16 in four patients (3%); 11q23 rearrangements in two patients (2%) and del(5q), in one patient (1%). The remaining 16 patients had miscellaneous clonal abnormalities. Specific translocations associated with the FAB type were found: t(8;21) with AML2 and t(15;17) with AML3. We concluded that our study in a Tunisian population confirmed the relation between some specific abnormalities and the FAB classification. We found a higher incidence for t(8;21) than usually described.     

A Service for Human Chromosome Studies in Saskatchewan

A service has been developed in Saskatchewan to make available the results of studies of human chromosomes, the material being forwarded to the laboratory by local transport facilities. During the first year of this project chromosome studies were requested for five doubtful cases of trisomy-21 (two were found to be normal) and for 20 definite cases of trisomy-21 in young patients (two had translocations but the parents of both these children had normal karyotypes). Eleven confirmed cases of Turner''s syndrome, two of Klinefelter''s syndrome, and one each of the D and E syndromes were also studied. The largest group for which studies were requested comprised 36 patients with mental retardation; only two abnormal karyotypes were encountered in this group.     

Karyotype analysis of B-Lymphocytes transformed by Epstein-Barr virus in 21 patients with B cell chronic lymphocytic leukemia

The karyotypes of 21 patients with chronic B cell leukemia were studied using lymphoblastoid cell lines obtained with the aid of the Epstein-Barr virus. Ten patients had a normal karyotype and eleven patients, an abnormal. There is no single characteristic anomaly, but certain types were more frequent, i.e., 14q+ as a result of a translocation 11;14, trisomy 12, and an isochromosome 17q. Abnormalities in these same three chromosomes have been found in other hematologic malignancies. It is postulated that loci with control cell proliferation are present on chromosomes 12, 14, and 17.     

A cytogenetic study directly from chorionic villi of 140 spontaneous abortions

Summary Spontaneous abortions were studied by analyzing chromosomes directly from chorionic villi. The frequency and the type of anomalies detected among 140 abortuses are in good agreement with those observed by others using conventional tissue cultures. Abnormal karyotypes were found in 48.6% of the cases. Trisomy predominated (66.2%), followed by polyploidy (22.1%), monosomy X (7.4%), and structural anomalies (4.4%). Among the trisomies, the most prevalent were of chromosome 22 (22.2%), 16(22.2%), and 13 (9.5%). The relative frequencies of trisomies, monosomy X, and the different chromosomes involved in trisomies seem to differ between our study and those in which tissue cultures were analyzed. Our low frequency of 45,XO karyotypes and the shift to trisomies of chromosomes whose involvement increases steeply with maternal age are considered due to the approximately 3 year higher mean maternal age in our sample. The sex ratio (male to female) in chromosomally abnormal abortuses was 1.28, which is nearly identical to the 1.2 found in earlier studies. Surprisingly, in chromosomally normal abortions males were significantly outnumbered by females (sex ratio 0.76). Since maternal cell contamination cannot have influenced the sex ratio in our study, we consider it worthwhile to investigate whether failures associated with X inactivation are responsible for pregnancy wastage of some euploid female conceptuses. Knowledge of the karyotypes may serve as a prerequisite for the investigation of non-chromosomal genetic causes of pregnancy wastage.     

Cohesinopathies: One ring, many obligations

Over 75 years ago, two human genetic disorders were initially described and named for their founding physicians: Cornelia de Lange (CdLS) and Roberts syndrome (RBS)/SC Phocomelia (SC). In the past 4 years, genetic studies of patients have revealed the primary genes involved in these disorders are the essential, evolutionarily conserved components of the cohesin pathway. This pathway serves to facilitate cohesion between replicated sister chromatids, thereby enabling proper chromosome segregation. As a result of these findings, these disorders now represent a novel class of human genetic disorders known as cohesinopathies. Over 60% of CdLS patients examined have de novo mutations in either: SCC2/NIPBL, SMC1, or SMC3, whereas the causative gene in Roberts syndrome and SC Phocomelia has been identified as ESCO2. Now modern genetic, biochemical, and cell biological approaches may be applied to determine the underlying mechanism of these genetic disorders.     

Partial trisomy of distal 5q and partial monosomy of Xp as a result of mating between two translocation carriers: a female with a balanced translocation t(X;5)(p11;q31) and a male with a der(13;14)(q10;q10)--a case report and a family study

This paper presents the family of a dysmorphic child with the phenotypic features of Turner's syndrome and 5q trisomy, whose parents are both carriers of a balanced translocation. The parents' karyotypes are 46,X,t(X;5)(p11.1;q31) and 45,XY,der(13;14)(q10;q10), respectively.     

Cytogenetic findings in Serbian patients with Turner's syndrome stigmata

Cytogenetic findings are reported for 31 female patients with Turner's syndrome. Chromosome studies were made from lymphocyte cultures. Non-mosaicism 45,X was demonstrated in 15 of these patients, whereas only three were apparently mosaic. Eight patients showed non-mosaic and four patients showed mosaic structural aberrations of the X-chromosome. One non-mosaic case displayed a karyotype containing a small marker chromosome. Conventional cytogenetics was supplemented by fluorescence in situ hybridization (FISH) with an X-specific probe to identify the chromosomal origin of the ring and a 1q12-specific DNA probe to identify de novo balanced translocation (1;9) in one patient. To our knowledge, this is the first finding of karyotype 45,X,t(1;9)(cen;cen)/46,X,r(X),t(1;9)(cen;cen) in Turner's syndrome. The same X-specific probe was also used to identify a derivative chromosome in one patient.