We report on two sibs with ICF syndrome (immunodeficiency, centromeric heterochromatin instability, and facial anomalies) diagnosed in the elder brother based on the typical chromosomal abnormalities present in 56% of metaphases from cultured lymphocytes. In a previous cytogenetic analysis this diagnosis had been missed due to low manifestation of the ICF chromosomal phenotype. Hypomethylation of classical satellites 2 and 3, and of α‐satellite DNA was shown in the lymphocytes of the younger sister. At 7 years of age the boy presented with hemiplegia due to tumerous invasion of the right brachial plexus. Histopathology revealed classical Hodgkin lymphoma, a neoplasia which might have been facilitated by the underlying genetic defect. © 2007 Wiley‐Liss, Inc.

We describe a familial interstitial deletion of 7.7-Mb involving Xp22.2-22.3. The deletion was transmitted from an asymptomatic mother to her two children with severe developmental delay, no speech development and autistic behavior. Assessment of the deletion boundaries by FISH and PCR analyses indicated that the deletions encompasses 27 genes. Several of these genes are associated with known disorders, like KAL1 (Kallmann syndrome), steroid sulfatase (STS) (X-linked ichtyosis), and arylsulfatase E (ARSE) (chondrodysplasia punctata). The deletion also includes all four VCX genes (VCX-A, VCX-B1, VCX-B, and VCX-C) and the neuroligin 4 (NLGN4) gene. VCX-A deficiency has been shown previously to be associated with mental retardation and NLGN4 mutations lead to mental retardation in conjunction with autism. Functional deficiency of both MRX genes, VCX-A and NLGN4, are most likely associated with the impaired cognitive development of the patients described here. The phenotype associated with the Xp deletion was highly variable in female carriers and might be attributed to unfavorable X inactivation. However, all the 27 genes included in the deleted interval escape X inactivation and are expressed at variable levels from the normal X chromosome. Thus, the overall X inactivation pattern and inter-individual expression variability of the genes in distal Xp might be determinants of the phenotype associated with the deletion.

We report on a 5.5-year-old girl with dysmorphic features and psychomotoric developmental delay with a mitotically stable supernumerary marker chromosome. The origin of the marker was identified by microdissection and reverse painting of marker DNA as the pericentromeric region of chromosome 1. Fine mapping by FISH with selected YAC or BAC clones identified no p-arm material on the marker. The marker has retained its original centromere and euchromatin from 1q21.1-q21.3 but only small remnants of the 1q12 heterochromatin. Furthermore, some FISH clones presented single signals on the marker and others presented double signals indicating a partial duplication within the marker. These observations suggest a multi-step origin of the marker most probably with ring formation as the first step.

AbstractObjectivesTo present the clinical, cytogenetic, and molecular cytogenetic findings of prenatally diagnosed interstitial deletion 10q25.2‐q26.1. The majority of distal 10q deletions are pure terminal deletions with breakpoints in 10q25 and 10q26. Only four patients have been described so far with interstitial deletions involving bands 10q25.2‐q26.1.MethodsPostmortem physical examination and autopsy of the foetus after medically terminated pregnancy. GTG‐banding, reverse painting, and FISH analysis with BAC clones on amniocyte metaphases were performed to determine the extent of the deletion.ResultsAt 20 weeks the eutrophic female foetus showed pronounced microretrogeny and hypertelorism, clubfeet as well as minor internal anomalies like pancreas anulare, atypically lobed liver, and missing choleocystis. Cardiac anomalies were not observed and the genitalia were of a normal female. The deletion encompasses 6‐Mb and is associated with hemizygosity for 30 genes, including the genes for beta‐tectorin, the beta‐1 adrenergic receptor, and the alpha‐2A adrenergic receptor.ConclusionAn interstitial deletion del(10)(q25.2q25.3 ∼ 26.11) was confirmed by FISH with mapped BAC clones. Clinical and molecular cytogenetic analyses of further interstitial 10q deletions are necessary to assess whether the phenotypic manifestations differ between deletions that are interstitial compared to those that include also the terminal region of chromosome 10. Copyright © 2005 John Wiley & Sons, Ltd.

A child with complete triploidy is rarely born alive. However, owing to the advances in perinatal medicine even extremely immature preterm infants receive full support in the delivery room and are admitted to the neonatal ICU. Consequently, the clinician may also have to consider the diagnosis of triploidy when faced with a dysmorphic extremely preterm infant. We report here the smallest described live born girl of 25 + 5 weeks of gestational age with typical clinical findings of complete triploidy phenotype II. The aim of the case report is to make the neonatologist aware of this syndrome using photographs of this case as well as discussing the literature available. Prompt clinical diagnosis confirmed by chromosome analysis helps doctors and parents with the decision whether to continue promising or to limit futile life support measures.

We describe the case of a 6‐month‐old boy with psychomotor retardation, craniofacial dysmorphism, cleft lip and palate, as well as hearing and visual impairment. Analysis of G‐banded chromosomes of the propositus showed a de novo interstitial deletion of the short arm of chromosome 12, del(12)(p12.1p12.3). Molecular cytogenetic analysis with bacterial artificial chromosomes (BAC) clones was used to refine the extent of the deletion. The deleted segment encompasses about 12.5 Mb between markers D12S1832 and G62375. The phenotypic consequences of the deletion are discussed and compared with other cases of interstitial deletions of proximal chromosome 12p. © 2002 Wiley‐Liss, Inc.

Constitutional de novo interstitial deletion of 8 Mb on chromosome 22q12.1-12.3encompassing the neurofibromatosis type 2

Zusammenfassung Hintergrund. Es wird über eine 21 Monate alte Patientin mit einer partiellen Trisomie 11q23–q25 (und einer telomernahen Deletion 11q24.3) berichtet, die aufgrund einer De-novo-Duplikation dieses Chromosomensegments entstanden ist. Dies stellt eine sehr seltene Chromosomenaberration dar. Fallbericht. Die Patientin zeigt klinisch typische morphologische Auffälligkeiten des Gesichts, Muskelhypotonie, eine allgemeine psychomotorische und mentale Retardierung, Mikrozephalie, Hinweise für Gyrierungs- und Myelinisierungsstörungen, einen Hörverlust, eine Hypothyreose, rezidivierende Infektionen der Atemwege, des Intestinaltrakts und der Harnwege bei einem VUR Grad 2–3 und einer Hydronephrose, eine Gedeihstörung und als besonders bedeutsame Störung Veränderungen im Larynx- und Bronchialbereich, die bei der flexiblen Bronchoskopie darstellbar waren und in dieser Form bisher nicht beschrieben wurden. Im frühen Säuglingsalter musste eine Behandlung wegen Apnoen, Hypoglykämie, Thrombopenie und Krampfaktivität im EEG durchgeführt werden. Pränataldiagnostik. In Kenntnis der speziellen chromosomalen Störung ist eine Pränataldiagnostik möglich, allerdings ist bei normalen Chromosomenbefunden der Eltern das Wiederholungsrisiko sehr gering.

Background. Report of a 21 month old female patient with a partial trisomy 11q23-q25 (and a deletion 11q24.3), which is not due to a chromosomal translocation in one of the parents, but represents a new duplication of that segment of chromosome 11. This is a very rare event.Case report. The patient's clinical symptoms consist of a typical dysmorphism of facial structures, muscle hypotonia, severe psychomotor and mental retardation, microcephaly and signs of abnormal brain structure, hearing loss, hypothyroidism, recurrent infections of the respiratory, alimentary and urinary tract, vesico-ureteral reflux and hydronephrosis, growth retardation and especially several important defects in the respiratory tract, visible in flexible brochoscopy, which were not reported before. In the neonatal period and during the first year treatment for apnoe, hypoglycemia, transient thrombocytopenia and a convulsive disorder was necessary.Prenatal diagnosis. Given the specific chromosomal changes, a prenatal diagnosis would be possible in future pregnancies, although the recurrence risk should be very low, considering the normal chromosomal findings in the parents.

A 12-year-old boy treated for SCID at 1 month of age by HLA-haploidentical BMT developed a lymphoproliferative disease of unknown etiology at the age of 9 years characterized by sustained, marked elevation of circulating CD8 + donor T cells and by diffuse infiltration of the liver by CD8 + T cells. Because of progressive liver disease, the patient underwent a second BMT from a younger HLA-matched sister. This treatment induced an effective graft-versus-graft reaction and led to complete replacement of the HLA-nonidentical, dysfunctional T cell system, resolution of the hepatopathy and full reconstitution of T and B cell functions. Bone Marrow Transplantation (2001) 28, 993–995.

We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively.

A permanent cell line, U-BLC1, was established from a primary transitional-cell carcinoma, TCC, of the urinary bladder. Karyotype analysis showed the line to be highly aberrant, with a near-triploid chromosome number of 68 to 73. Comparative genomic hybridization revealed some distinct differences between the primary tumor and the established cell line. Karyotype analysis showed 3 marker chromosomes with homogeneously staining regions, HSRs, in the cell line. The HSRs were isolated by microdissection and the microdissection probes were hybridized to normal metaphase chromosomes. The HSRs contain sequences known to be frequently involved in amplification in transitional-cell carcinoma of the bladder, 6p22, 7p11-p12, 9p23-pter, and one region not yet reported to be amplified in primary TCC of the bladder, 1p31-p32. A candidate-gene approach showed that in the region 7p11-p12 the EGFR locus is amplified and highly expressed.

Members of the long-range, low-copy-number repetitive DNA sequence family chAB4 are located on nine different human chromosome pairs and the Y chromosome, i.e. on the short arms of all the acrocentrics. To localize the chAB4 sequences more precisely on the acrocentrics, chAB4-specific probes together with rDNA and a number of satellite sequences were hybridized to metaphase chromosomes of normal probands and of carriers of Robertsonian translocations of the frequent types rob(13q14q) and rob(14q21q). The results demonstrate that chAB4 is located on both sides of the rDNA on all the acrocentrics; the exact location, however, may be chromosome specific. Chromosome 22, most probably, is the only chromosome where chAB4 is found in the direct neighbourhood of the centromere. Fluorescence in situ hybridization analyses of metaphase chromosomes of carriers of rob(21q22q) revealed breakpoint diversity for this rare type of Robertsonian translocation chromosome. A direct involvement of chAB4 sequences in recombination processes leading to the Robertsonian translocations analysed in this study can be excluded.

Three new cases of true mosaic trisomy 17 (MT17) were diagnosed in amniotic fluid cells. Postnatal chromosome analysis from lymphocytes did not confirm the trisomic cell line, and follow‐up studies showed normal psycho‐motor development of the children, in one case up to the age of 4½ years. We suggest that there are similarities between MT17 and MT20, in which the majority of pregnancies result in deliveries of healthy babies. Copyright © 1998 John Wiley & Sons, Ltd.

61 fetuses/newborns who had an aberrant karyotype in amniocentesis (BC) or percutaneous umbilical blood sampling (PUBS) were followed-up by chorionic villus sampling (CVS) at birth or after interruption. The overall rate of discrepancies is surprisingly high. Among 46 cases with a non-mosaic numerical aberration in AC or PUBS three had a discrepant finding in placental tissue. This was also true in one of seven cases with non-mosaic structural aberrations and in three of five cases with mosaic structural aberrations. All three cases with a mosaic numerical aberration in AC or PUBS were not represented by CVS and/or lymphocytes or fibroblasts, demonstrating the general problem of the unpredictable prognostic value of mosaicism. Our data suggest, that in case of prenatal diagnosis by CVS, using a combined procedure of short-term (STC) and long-term culture (LTC), in our sample we would have missed one case of 45,X (1.6 per cent). When relying only on STC another two cases, one with 47, +21 and one with 46,XX,der(22) would not have been recognized (4.9 per cent, n=3). All other chromosome aberrations would have been detected by STC alone. On the other hand, one case of 45,X was 'nearly missed' because of low-grade mosaicism in AC (45,X[1]/46,XX[19]), whereas in placental tissues and PUBS only 45,X was represented. This study mimics a false-negative rate of about 1:3000 (STC plus LTC) or about 1:1000 (STC alone) for an a priori risk group of two per cent (e.g., advanced maternal age). Copyright (C) 1998 John Wiley & Sons, Ltd.

We describe a case of apparent trisomy 21 that does not fulfill the criteria for the clinical diagnosis of Down's syndrome (DS). Our patient was subjected to karyotype analysis and found to have full, non-mosaic trisomy 21 in both blood lymphocytes and skin fibroblasts, while examination of the term placenta, which was performed earlier in the course of a different study, had shown mosaicism (73%) for trisomy 21. FISH analysis showed no obvious rearrangement of the DS chromosomal region in any of the chromosomes 21. Molecular analysis using polymorphic markers on chromosome 21 verified the existence of trisomy for the entire long arm of the chromosome and showed that the origin of the extra chromosome was maternal and was probably the result of a mitotic error. In contrast with the above, the clinical evaluation using the Jackson checklist of 25 signs failed to establish the diagnosis of DS. We believe that our patient might present mosaicism in other tissues that are not available for analysis and can be regarded as an extreme example in the continuous spectrum of karyotype phenotype associations in mosaic cases.

An uncommon coexistence of circumscribed hyperpigmentation and hypopigmentation, in close proximity to each other, is described in a 17 years old patient with various other cogenital defects, such as dysmorphic facial appearance, severe kyphoscoliosis, delayed motor development, epileptic seizures, and mental retardation. We suggest the combination of hyper- and hypopigmented cutaneous lesions is an example of allelic twin spotting. Because the skin of this patient showed three different degrees of pigmentation the term "cutis tricolor" is proposed.

We report on a 19-week-old fetus with a 46,XX karyotype, normal female external genitalia, complete gonadal agenesis, large encephalocele, spina bifida, and omphalocele. We postulate a new syndrome. Hitherto no consistent malformation patterns have been observed in agonadism patients. True agonadism, including even the unusual finding of an XX gonosomal status, is obviously not as rare as suggested.