Virilization of the external genitalia and severe mental retardation in a girl with an unbalanced translocation 1;18.

A female infant with dysmorphic facial features, psychomotor retardation, and clitoris hypertrophy is described. Molecular cytogenetic analyses revealed a de novo unbalanced translocation, causing partial monosomy 1p36 and partial trisomy 18q22. Monosomy 1p was confirmed by FISH, and trisomy of the distal part of chromosome 18q was demonstrated by microFISH. Gene copy number changes in these chromosomal regions were determined by array-CGH. The absence of a number of facial dysmorphic signs, and the presence of clitoris hypertrophy indicate that the combination of a del(1p36->pter) with a dup(18q22->qter) may lead to a unique phenotypic constellation. The findings at birth and at age 12 years in our patient are compared with genotype-phenotype correlations discussed in the literature.

Report of a patient with a trisomy of chromosome region 20q11.2-->20q12 and characterization with FISH.

We report on a 16-month-old boy presenting with psychomotor retardation, craniofacial anomalies and severe vision deficit. Analysis of GTG-banded chromosomes showed that the patient had extra chromosomal material in the long arm of one chromosome 20. This chromosome aberration was further characterized with FISH using a chromosome 20 specific paint and band-specific probes. A partial trisomy 20q was shown to be present, the karyotype being 46, XY, dup (20) (q11.2q12). The cytogenetic and clinical findings are compared with cases previously reported in the literature.

De novo "pure" partial trisomy (6)(p22.1-->pter) in a chromosome 15 with an enlarged satellite, identified by microdissection.

We report on a newborn boy with a congenital heart defect, severe pre- and postnatal growth retardation, feeding problems, facial anomalies and unilateral hydronephrosis. Cytogenetic analysis showed extra chromosomal material on the short arm of one chromosome 15 that at first sight could be mistaken for a chromosomal variant and could not be identified with conventional banding techniques. Chromosome analysis of the parents showed that both had a normal karyotype. Microdissection of five copies of the aberrant chromosome 15, amplification of the dissected chromosomal material by DOP-PCR and subsequent reverse painting was performed and disclosed that the patient had a de novo 46,XY,der(15)(6pter-->6p22.1::15p12-->15qter) karyotype with a "pure" trisomy of chromosome region 6p22.1-->6pter. The associated phenotypic anomalies are compared with other reported cases with a distal duplication of chromosome 6p.

De novo duplication (5)(q31.3q33.3): report of a patient and characterization of the duplicated region using microdissection and FISH.

We report on a 2-year-old boy presenting with growth and psychomotor retardation and facial anomalies, including a flat face with prominent forehead, a flat nasal bridge and flat occiput, unusually long curved eyelashes, and a thin upper lip with down-turned corners of the mouth. Analysis of GTG-banded chromosomes demonstrated that the patient had extra chromosomal material in the long arm of one chromosome 5. This chromosome aberration was characterized further using microdissection and FISH with band-specific probes and a de novo direct duplication (5)(q31.3q33.3) was shown to be present. We have compared this case with others known to be partially trisomic for chromosome 5q reported in the literature.

Interstitial deletion of the short arm of chromosome 8: report of a patient and review of the literature.

We report a mentally retarded girl with minimal dysmorphic signs. Cytogenetic examination showed an interstitial deletion of chromosome 8: 46, XX, del(8)(p21.2p22). This deletion has not been reported before. We compare the patient with the literature data.

Striking facial dysmorphisms and restricted thymic development in a fetus with a 6-megabase deletion of chromosome 14q.

During routine ultrasound screening at 12 weeks 5 days of gestation, a nuchal translucency of 7 mm, an omphalocele, and fetal hydrops were found and prompted chorionic villus sampling at 13 weeks 2 days. Chromosome analysis showed an unbalanced karyotype with an abnormal chromosome 14. The mother was a carrier of a translocation karyotype 46,XX,t(13;14) (q34;q32.2). In the fetus this gave rise to a partial trisomy 13q and partial monosomy 14q (fetal karyotype: 46,XX,der[14]t[13;14][q34;q32.2]). By Array-CGH on DNA extracted from a postmortem skin culture, a duplication of approximately 1.7 Mbp of the distal part of chromosome 13q34 and a deletion of approximately 6.0 Mbp of the distal part of chromosome 14q32.2 was demonstrated. Postmortem findings after termination of pregnancy at 14 weeks 6 days included, among others, a severe hypoplasia of the median part of the maxilla, no recognizable nose, a broad median palatoschisis, nonlobulated lungs, a horseshoe kidney with multicystic dysplasia, and decreased development of cortical cellularity in the thymus. These clinical manifestations and autopsy findings of the fetus are compared with those of previously published cases and the possible involvement in this pathology of the YY1 and JAG2 transcription factors and the BCL11b and SIVA-1 regulators of thymic development is discussed.

Characterization of partial trisomy 9p due to insertional translocation by chromosomal (micro)FISH.

We describe a family with an insertion 12;9 translocation occurring in a balanced form in a mother and two sons, but in an unbalanced form in the proband, resulting in trisomy of chromosome region 9p22-->9p24. The proband manifests typical features of trisomy 9p; the clinical signs were mental and growth retardation, microcephaly, epicanthus, low-set ears, micrognathia, clinodactyly and hypoplastic phalanges of the fifth fingers, hypoplasia or absence of toenails, and extremely small genitals. The GTG-banded findings were confirmed using (micro)FISH. Intriguingly, the mother and the two carrier sons exhibited major learning difficulties that were not present in the non-carrier sister of the mother: this may be due to a gene disruption or induction of abnormal expression. Dysmorphic features were not present in the three carriers. We compare our clinical and cytogenetic findings with other cases of partial trisomy 9p reported in the literature.

Partial trisomy of the short arm of chromosome 18 due to inversion duplication and direct duplication.

We report one patient with a de novo inversion duplication 18 (pter-->cen) and two cases of direct tandem duplication 18 (pter-->cen), one due to maternal inheritance and the other arising as mosaicism of unknown origin. The duplications are demonstrated by high resolution banding. They were verified by in situ hybridization with a paint specific for chromosome 18 and with DNA probe LI.84 specific for the centromere region of chromosome 18. FISH with the genomic DNA probe pHRR68 specific for 18p11.32 revealed a subtle deletion concomitantly involved in the case of inversion duplication 18p. The patients exhibit slight developmental delay/moderate mental retardation and only a few dysmorphic features. The literature on trisomy 18p is reviewed and the present cases are compared to it.

Mosaic trisomy 11p in monozygotic twins with discordant clinical phenotypes.

We report on monozygotic (MZ) twins with a de novo mos 46,XX,der(15)t(11;15)(p12;p11.2)/46,XX karyotype varying in different tissues. The clinical presentation and findings at the cytogenetic level are described. One of the infants had definite minor anomalies at birth, also found in other cases of trisomy of 11p resembling the Beckwith-Wiedemann syndrome. Theoretical backgrounds regarding the string of events leading to the cytogenetic findings in these twins and the various factors that might have contributed to the dissimilarities in phenotype between these twins are discussed.

Intrachromosomal insertion translocation resulting in duplication of chromosome band Yq11.2 in two fertile brothers.

Chromosome analysis in a couple referred because of two spontaneous abortions showed a normal 46,XX karyotype in the 28-year-old female and an aberrant Y chromosome with an enlarged short arm in the 30-year-old male. Subsequent chromosome analysis showed that his 33-year-old brother was carrier of the same Y chromosome aberration. Further characterization of the aberrant Y chromosome with FISH using probes specific for chromosome bands Yp11.32, Yq11.2, the centromere and the subtelomeric region of the p-arm of the Y chromosome showed that chromosome band Yq11.2 was duplicated and inserted in the p-arm of the Y chromosome. Combining the results of the analysis of GTG-banded chromosomes and of the FISH analysis we conclude that both patients have a 46,X,ins dup(Y)(pter --> p11.23::q12 --> q11.1::p11.23 -->) karyotype. The clinical and cytogenetical findings are reported and discussed.

Prenatal detection of complex chromosomal aberrations using advanced molecular cytogenetic techniques.

OBJECTIVE: This study aimed to identify a marker chromosome and characterize the short arm of a derivative chromosome 5 in a foetus with the following karyotype: mos 47,XX,del(5)(p?),+i(5)(p10)[50]/48,XX,del(5)(p?),+i(5)(p10),+mar[25]. METHOD: Amniocentesis was performed in the 26th week of pregnancy because of ultrasound abnormalities (polyhydramnion and decreased amount of gastric filling). All classic banding techniques were performed. FISH and microdissection combined with reverse painting were used to reveal the exact origin of the marker and any extra material on the deleted chromosome 5p. The parents decided to continue the pregnancy and we compared the clinical features of the child born in week 34 with data from the literature on trisomy 5p. The possible contribution of trisomy of the centromeric region of chromosome 8 and trisomy 8p23.3-->8pter to this clinical picture was evaluated. RESULTS: GTG banding showed one normal and two aberrant chromosomes 5 [del(5)(p?) and i(5)(p10)] in all the cells examined. Furthermore, a supernumerary marker chromosome was present in approximately 30% of the cells. The marker was CBG positive and positive with the pancentromere probe, but dystamicinA/DAPI negative. It did not contain NOR-positive satellites. FISH proved this marker to be derived from the centromeric region of chromosome 8. MicroFISH disclosed the aberrant chromosome 5 as der(5)t(5;8)(p10;p23.3). The parent's karyotypes were normal. The baby showed the characteristic features of trisomy 5p syndrome. She died at the age of 15 days after cardiorespiratory arrest. CONCLUSION: The karyotype was interpreted as mos 47,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10) (WCP5+,D5S23+)[50]/48,XX,add(5)(p10).rev ish der(5)t(5;8)(p10;p23.3),+i(5)(p10)(WCP5+,D5S23+),+mar.ish 8(p10q10)(D8Z2+,WCP8-)[25]. Therefore, the baby had complete trisomy 5p, with trisomy of the distal part of 8p and of the centromeric region of chromosome 8. The clinical significance of de novo marker chromosomes is a major problem in prenatal counselling. Molecular cytogenetic tools such as FISH and microFISH are indispensable for characterizing markers and determining the breakpoints more precisely in deleted chromosomes.

Familial insertion (3;5)(q25.3;q22.1q31.3) with deletion or duplication of chromosome region 5q22.1-5q31.3 in ten unbalanced carriers.

We report on the clinical and cytogenetic data of a large family with an unbalanced insertion translocation (3;5)(q25.3;q22.1q31.3). Analysis of GTG-banded chromosomes demonstrated that unbalanced inheritance of a parental insertion translocation caused either a partial deletion or duplication 5q in this family. The derivative chromosomes were characterized further using microdissection and FISH with band-specific probes. The clinical picture of the proband with a partial deletion of chromosome 5 was characterized by moderate psychomotor retardation, mild facial dysmorphism, cleft palate, and single transverse crease. The family members with a partial duplication of chromosome 5 were borderline intelligent, had mild facial dysmorphism, a cardiac anomaly, and a high-pitched voice. The unbalanced carriers were compared with patients reported in the literature with a duplication or deletion of chromosome region 5q22.1 --> 5q31.3.