Prenatal diagnosis and molecular cytogenetic characterization of mosaic ring chromosome 13

We present prenatal diagnosis and molecular cytogenetic characterization of de novo mosaic r(13). A 32-year-old woman underwent amniocentesis at 18 weeks of gestation because of maternal anxiety. Amniocentesis revealed a karyotype of 46,XY,r(13)[33]/45,XY,-13[19]. aCGH on uncultured amniocytes at repeated amniocentesis detected a 4.22-Mb deletion at 13q34. Interphase FISH on 100 uncultured amniocytes showed the ratio of r(13):-13:idic r(13) as 85%:13%:2%. The cord blood had a karyotype of 46,XY,r(13)[91]/46,XY,idic r(13)[6]/45,XY,-13[3]. The placenta had a karyotype of 46,XY,mar(13)[31]/45,XY,-13[3]. Metaphase FISH confirmed that the marker chromosomes in placenta were derived from chromosome 13. aCGH on cultured placental cells detected a 77.81-Mb deletion at 13q13.3–q34. The fetus postnatally manifested facial dysmorphism. Prenatal diagnosis of r(13) should alert mosaicism for deletion/duplication of r(13) and distal 13q deletion. Fetoplacental chromosomal discrepancy of r(13) may exist in case of mosaic r(13) detected by amniocentesis.     

The fetal phenotype of the 18p-syndrome. Report of a male fetus at twenty-one weeks

Morphological and cytogenetic findings in a male fetus at 21 weeks gestation after prenatally detected monosomy 18p are reported. The fetus displayed dysmorphic features resembling the 18p-syndrome, such as decreased head circumference, slightly receding forehead, hypertelorism, epicanthus, horizontal palpebral fissures, depressed nasal bridge, long philtrum, carp mouth, irregular crenated maxillar alveolar ridge, retrognathia, lowset dysplastic ears with posterior rotation, edema of neck, hands and feet respectively, fingers with drop-shaped tips, short first toes with dysplastic nails, hypoplastic male external genitalia. After termination of the pregnancy, biopsies from different fetal organs as well as from the placenta were taken and set up for long term cell cultures. The metaphases of fetal organs all showed the karyotype 46,XY,18p-. A fetal blood culture failed to grow. Unexpectedly, the metaphases of the placenta showed the mosaic karyotype 46,XY/46,XY,18p-/46,XY,18p+.     

Placental alkaline phosphatase types in Germany

Summary Two children with autosomal deletion (46,XY,del(12)(p11) and 46,XY/46,XY, del(5)(p13)) and normal phenotype were found among 5049 consecutive newborn children. The mother of the proband with deletion short arm 5 had the karyotype 46,XX,9qh+, but the parents had otherwise normal chromosome constitution.

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Zusammenfassung Zwei Kinder mit autosomaler Deletion (46,XY,del(12)(p11) und 46,XY/46,XY,del(5)(p13)) bei normalem Phänotyp wurden unter 5049 auslesefrei gewonnenen Neugeborenen entdeckt. Die Mutter des Probanden mit der Deletion am kurzen Arm von Nr. 5 hatte den Karyotyp 46,XX,9qh+; sonst hatten die Eltern normale Chromosomen.

     

Lymphocyte chromosome survey in 42 patients with retinoblastoma: Effort to detect 13q14 deletion mosaicism

Summary The results of a lymphocyte chromosome survey of retinoblastoma (Rb) patients using a method able to detect a relatively low proportion mosaicism of 13q14 deletion are presented. Three out of 42 Rb patients had abnormal karyotypes; two mosaic cases with the karyotype 46,XY,del(13) (q14.1q14.3)/46,XY and 46,XX,del(13)(q14.1q14.3)/46,XX(the proportions of 13q14-cells, 51% and 9%, respectively), and the other with the karyotype 46,XY,del(13)(q14.1q21.2). All of these three cases had bilateral sporadic Rb. Two mosaic cases had an apparently normal phenotype except for Rb. These data suggest that the frequency of Rb cases with a 13q- cell line in lymphocytes may be greater than that which has been reported.     

Deletion - translocation del (12) (p11) leads to (t10;12) (p13;pII).

Renewed examinatinon with improved banding techniques of a boy previously reported to have the karyotype 46, XY,del(12)(p11) revealed a translocation 46, XY,t(10;12)(p13;p11), and reexamination of a boy previously reported to have the karyotype 46,XY/46,XY,del(5)(p13) showed the same mosaicism, but with a significantly lower frequency of cells with del(5)(p13), 8% compared with 23% at the time of birth. The decrease of the frequency of cells with chromosome abnormality in mixoploids during the first years of life as found in the present case as well as in prevously reported cases is discussed.     

A new inherited interstitial deletion of the distal long arm of chromosome 4

A 12-year-old boy showed mild dysmorphic features, late presentation of learning difficulties and behaviour problems, obesity, breast hypertrophy and bilateral slipped capital femoral epiphysis. His mother also has mild dysmorphic features, obesity, and a similar history of late presentation of learning difficulties and behaviour problems. Cytogenetic analysis demonstrated an inherited distal long arm deletion of one chromosome 4. The boy's karyotype was interpreted as 46,XY,del(4)(q32 q33)mat and the mother's karyotype as 46,XX,del(4)(q32 q33). This is the second report of an inherited distal 4q deletion and the first report of interstitial chromosome 4 deletion involving q32 q33 segments.     

Partial monosomy of the long arm of chromosome 16: A distinct clinical entity?

Summary A 7-month-old male child with a de novo, seemingly belanced reciprocal 5p/16q translocation and karyotype 46,XY,t(5;16) (p14;q21), resulting from a maternal meiotic error, is described. The clinical findings in this patient are strikingly similar to those in the only patient with partial deletion 16q hitherto described, [del(16)(q21)], indicating that during the 5p/16q rearrangement, 16q material was lost and suggesting that partial or total deletion of the long arm of chromosome 16 distal to band q21 is accompanied by a distinct clinical phenotype.     

Mapping of the gene for glutathione reductase on chromosome 8.

Red cell glutathione reductase (E-GSR) activity in 3 patients with mos46,XY/47,XY,+8 was higher than the mean value in controls, confirming the previous assignment of the E-GSR locus to chromosome 8. In a infant with a terminal deletion of the short arm of chromosome 8, 46,XX,del(8)(:p21 leads to qter), E-GSR activity was markedly lower than in infant controls. The authors suggest that the E-GSR locus is in the region 8p21 leads to pter.     

Chromosome duplications and deletions and their mechanisms of origin.

Duplications and deletions of the same gene loci or chromosome regions are known to produce different clinical manifestations and are significant factors in human morbidity and mortality. Extensive cytogenetic and molecular cytogenetic studies with cosmid and YAC probes in two patients with unique mosaicism for reciprocal duplication-deletion allowed us to further understand the origin of these abnormalities. The first patient's mosaic karyotype was 46,XX, inv dup(11) (q23q13)/46,XX,del(11)(q13q23). The second patient had a 46,XY,dup(7)(p11.2p13)/46,XY,del(7)(p11.2p13)/46,XY karyotype. Fluorescence in situ hybridization studies on the first patient placed the two breakpoints near the folate-sensitive fragile sites FRA11A and FRA11B. The presence of repeated sequences responsible for these fragile sites may have been involved in the patient's duplication-deletion. Our investigation leads us to conclude that, in addition to known mechanisms (such as unequal crossovers between homologs, unequal sister chromatid exchanges, excision of intrachromatid loops, and meiotic recombination within a single chromatid), duplication-deletion can also arise by the formation of an overlying loop followed by an uneven crossover at the level of the DNA strand.     

Prenatal diagnosis of de novo unbalanced translocation 8p;21q using subtelomeric probes

We report an unbalanced translocation involving chromosomes 8 and 21 in a fetus showing ultrasonographic abnormalities in the second trimester of pregnancy. A 41-year-old pregnant woman, gravida 1 para 0, was referred to the Genetics Clinic at the 16th week of gestation because of advanced maternal age and fetal pelvicaliectasis on ultrasonographic examination. Pregnancy had occurred following ICSI treatment. After genetic counseling amniocentesis was performed. Fetal karyotype analysis revealed a 46,XY,8p+ karyotype. Ultrasonographic examination was repeated at the 20th week of gestation and showed intrauterine growth retardation, ventriculomegaly, cerebellar structural abnormality and pelvicaliectasis. Chromosomes of both parents were normal. Molecular cytogenetic studies (FISH) using chromosome-specific subtelomere probes showed a terminal deletion of 8p and trisomy of the 21q subtelomeric region. Further analysis with Down Syndrome specific region probes revealed two signals. The couple decided to terminate the pregnancy. This is the first prenatally diagnosed case of unbalanced t(8p;21q) of de novo origin.     

A craniosynostosis in a boy with a del(7)(p15.3p21.3): assignment by deletion mapping of the critical segment for craniosynostosis to the mid-portion of 7p21

Summary A tiny interstitial delection of 7p was found in a 5-month-old boy with a craniosynostosis and many anomalies. His karyotype was 46,XY,del(7)(p15.3p21.3). Here we present not only further evidence of an association between craniosynostosis and 7p monosomy, but also deletion mapping to indicate that the critical segment for craniosynostosis lies in the mid-portion of 7p21, that is at 7p21.2 or the proximal part of 7p21.3.     

Interstitial deletion of the short arm of chromosome 4. A phenotype distinct from the Wolf-Hirschhorn syndrome

In this paper we report a 3-month-old male newborn with marked hypotonia and an interstitial deletion of the short arm of chromosome 4 but with preservation of the 4p16 band (karyotype 46,XY,del(4)(pter----p15.3::p14----cen----qter). In contrast to patients with a pure 4p16 deletion this patient presented dysmorphic stigmata which were much more discrete than those found in the typical Wolf-Hirschhorn syndrome.     

Interstitial deletion of the band 4p15.3 defined by sequential replication banding

A 15-year-old boy with intellectual disability was found to have a de novo interstitial deletion in the short arm of chromosome 4. Using GTL banding and sequential replication banding the deleted band was found to be the more terminal of the two G dark sub-bands of 4p15, that is 4p15.3. The karyotype was defined as 46,XY,del(4)(p15.2p16.100). To our knowledge this specific deletion has not been previously described.     

Interstitial delection of the long arm of chromosome 8

Summary This report describes a polymalformed 18-month-old male with an interstitial deletion of the long arm of chromosome 8. His karyotype is: 46,XY,del(8)(q21).     

Interstitial deletion of the short arm of chromosome 3

Summary A de novo interstitial deletion of the short arm of chromosome 3 was prenatally diagnosed in a male fetus, karyotype 46,XY,del(3)(pterp14.2::p11qter). The fetus had craniofacial dysmorphisms, a single transverse palmar crease, ulnar deviation in the wrists, cardiovascular anomalies, a slight ureteric dilatation and a mobile caecum. Our observations are compared with five other cases with interstitial deletion of the short arm of chromosome 3 to delineate further the proximal 3p deletion syndrome. The gene for beta-galactosidase-1 (GLB-1) has previously been assigned to chromosome 3(p21q21). The absence of a gene dosis effect for GLB-1 in this study indicates exclusion of GLB-1 from 3(p11p14.2).     

Partial 1p monosomy in a physically and mentally retarded boy

An 8-year-old boy is reported with marked mental and physical retardation, microcephaly, hypertelorism, mongoloid palpebral fissures, hypoplasia of the maxillary portion of the face, and other discrete anomalies. Deletion of the distal portion of the short arm of the chromosome 1 and the karyotype 46,XY, del(1)(p33----pter) was detected.     

Molecular cytogenetic characterization of ring chromosome 4 in a female having a chromosomally normal child

We present the clinical and molecular findings of mosaic ring chromosome 4. The patient was referred to us for infertility and short stature. Results of three repeated cytogenetic analyses from lymphocytes showed a similar mosaic karyotype with multiple cell-lines [46,XX,r(4)/45,XX,-4/46,XX,dic r(4)/47,XX,r(4),+r(4)/46,XX]. FISH showed deletion of the 4p subtelomeric region and the 4q telomeric region from the ring chromosome 4. The breakpoints were mapped using molecular analysis. Parental karyotypes were normal. During the course of this study, the patient became pregnant without assisted reproductive technology. The result of amniocentesis performed at 16 weeks gestation showed a normal karyotype. Delivery was uncomplicated. This is the first report, to our knowledge, of the presence of ring chromosome 4 having various mosaic conditions in a female having a chromosomally normal fetus.     

Langer-Giedion syndrome,in a child with complex structural aberration of chromosome 8

A patient with typical features of the Langer-Giedion syndrome (tricho-rhino-phalangeal syndrome, type II) is described. In the karyotype an interstitial deletion of the long arm of chromosome 8 (band 8q22) was observed as the result of a complex rearrangement of chromosomes 1 and 8: 46,XY inv(8)(q23 leads to q242), del(8)(q221 leads to q223), ins(8;1) (q221;p321 p341;q242). Previously reported cases of Langer-Giedion syndrome with deletion of 8q are compared with the present one.     

Prenatally identified case of mosaicism of chromosome 16 trisomy

We present the prenatally identified case of mosaicism of chromosome 16 trisomy. A patient with the pregnancy complicated in the first trimester by the threat of breaking was refered to the high risk group according to the results of the screening program. The ultrasonic research revealed a number of phenotypical pathologies in 19-weeks-old fetus such as congenital heart disease (ventricular septal defect), hyperechoic bowel, single umbilical artery and some other ones. Cytogenetical and FISH analyses of the placental villi revealed karyotype with chromosome 16 trisomy. The further research of amniotic fluid cells revealed the karyotype of fetus as mos47,XX,+16 / 46,XX. The pathologoanatomic research of the abortus has verified the multiple congenital malformations.     

Extra copy of 20q deletion, acute myelomonocytic leukemia (M4) and Niemann-Pick disease

A 59-year-old hypertensive white male was diagnosed with acute myelogenous leukemia (AML), M4. A bone marrow aspirate showed a karyotype of 46,XY,del(20)(q11.2q13.3)[12]/ 47,XY,del(20)(q11.2q13.3)x2[8]. The majority of cases with 20q deletion are associated with myeloid disorders; however, an extra copy of the 20q deletion has rarely been reported. The patient expired seven days after admission to the hospital. At autopsy hepatosplenomegaly was present. Many foamy macrophages with bubbling cytoplasm in the spleen, liver, bone marrow and lymph nodes were suggestive of Niemann-Pick disease, type E. AML has not previously been reported with Niemann-Pick disease.