Maternal origin of a unique extra chromosome, der(9)(pter-->q13::q13-->q12:) in a girl with typical trisomy 9p syndrome

We report on a girl with the typical trisomy 9p syndrome who had an additional E-sized metacentric chromosome. On the basis of GTG- and CBG-banding, her karyotype was considered to be 47,XX,+der(9)(pter-->q13::q13-->q12:) de novo. Results of a fluorescence in situ hybridization study using a chromosome 9-specific painting probe were compatible with this cytogenetic interpretation. Molecular analyses of six highly polymorphic dinucleotide repeat loci on the short arm and the proximal long arm of chromosome 9 demonstrated that the girl inherited one allele from her father and two identical or different alleles from the mother. We speculated that the extra chromosome may have resulted from either nondisjunction of chromosome 9 followed by a U-type exchange and a crossing-over between different sister chromatids during maternal meiosis I and subsequent breakage and malsegregation during meiosis II, or nondisjunction during meiosis II followed by isochromosome formation in one of the two maternal chromosomes 9 and subsequent breakage.     

Tetrasomy 9p caused by idic (9) (pter→q13→pter)

Cytogenetic investigation on a malformed male infant showed an extra chromosome similar to chromosome 9 in all metaphases studied. GTG, CBG, and G-11 staining suggested that the extra chromosome was an abnormal 9, permitting the identification of the chromosome constitution as 47,XY, +idic (9) (pter→q13→pter).     

Monosomy 9p24→pter and trisomy 5q31→qter: Case report and review of two cases

Partial deletion of the short arm of chromosome 9 (p24→pter) and partial duplication of the long arm of chromosome 5 (q32→qter) were observed in an abnormal boy who died at age 8 weeks of a complex cyanotic cardiac defect. He also had minor anomalies, sagittal craniosynostosis, triphalangeal thumbs, hypospadias, and a bifid scrotum. Two other infants with similar cytogenetic abnormalities were described previously. These patients had severe congenital heart defect, genitourinary anomalies, broad nasal bridge, low hairline, apparently low-set ears, short neck, and triphalangeal thumbs, in common with our patient. We suggest that combined monosomy 9p23,24→pter and trisomy 5q31,32→qter may constitute a clinically recognizable syndrome. © 1995 Wiley-Liss, Inc.     

Combined trisomy 9 and Ullrich-Turner syndrome in a girl with a 46,X,der(9)t(X;9)(q12;q32) karyotype

Total trisomy 9 is a rare disorder with most patients dying before age 4 months. Herein, we report a 9-year-old girl with mental retardation, short stature, a peculiar face and other minor defects, who was diagnosed as having an unbalanced de novo X-autosome translocation with a 46,X,der(9)t(X;9) (q12;q32) karyotype resulting in almost a full trisomy 9(pter→q32) and a partial monosomy X(q12→pter). The clinical findings of our patient, almost exclusively resemble those of trisomy 9p and the Ullrich-Turner syndromes and has few manifestations of 9q trisomy. BrdU replication studies by Giemsa staining showed an earlier replication of 9p in the translocated chromosome, but a marked late-replication pattern for almost the complete 9q arm involved in the translocation. FISH studies confirmed the presence of three 9 centromeres, excluded the presence of the X centromere signal in the rearranged chromosome, and showed that both Xq telomeric sequences were present. BrdU replication studies by FISH showed an usual pattern of striking late-replication around the XIC of the derivative chromosome, but early replication of the chromosome 9p segment and distal Xq. Am. J. Med. Genet. 80:199–203, 1998. © 1998 Wiley-Liss, Inc.     

Trisomy 5q12→q13.3 in a patient with add(13q): Characterization of an interchromosomal insertion by forward and reverse chromosome painting

We report on a patient with azoospermia, mild mental retardation, and minor physical anomalies. Chromosome analysis demonstrated the presence of additional material on the long arm of one chromosome 13. Forward chromosome painting using chromosome-specific libraries showed an insertion of material from chromosome 5. Further characterization with flow sorting of the aberrant chromosome and amplification by DOP-PCR followed by reverse chromosome painting showed specific trisomy of 5q12→q13.3. Am. J. Med. Genet. 73:351–355, 1997. © 1997 Wiley-Liss, Inc.     

Molecular cytogenetic studies of duplication 9q32→q34.3 inserted into 9q13

Fluorescence in situ hybridization (FISH) studies using whole chromosome 9 painting probe, classical satellite (9q12-specific) probe and abl cosmid probe (locus: 9q34) were performed on a female infant who was born with multiple congenital anomalies and the karyotype 46,XX, 9q+. The results of FISH confirm the euchromatic nature of the extra material on the long arm of chromosome 9, and provide evidence that it is of chromosome 9 origin. The structural rearrangement has probably resulted from an insertion of a duplicated segment 9q32→q34.3 into band q13, as shown by the abl cosmid probe. The clinical features in this patient are similar to the previously reported cases of partial trisomy 9q3.     

Case of partial trisomy 9p and partial trisomy 14q resulting from a maternal translocation: Overlapping manifestations of characteristic phenotypes

We report on a female infant with partial trisomy 9p (pter→p13) and partial trisomy 14q (pter→q22) resulting from a 3:1 segregation of a maternal reciprocal translocation (9;14)(p13;q22). Both trisomy 9p and partial trisomy 14q have been described as recognized phenotypes with characteristic patterns of anomalies. This patient appears to be the first reported with a partial duplication of both 9p and 14q resulting in an overlapping phenotype including minor facial anomalies, cleft palate, and hand-foot anomalies. However, the facial findings were more pronounced than commonly observed in cases with only one or the other duplicated chromosome regions, resulting in a distinctive appearance. Am. J. Med. Genet. 84:132–136, 1999. © 1999 Wiley-Liss, Inc.     

Maternal complex chromosome rearrangement ascertained through a del (13)(q12.1q14.1) detected in her mildly affected daughter

A maternal complex chromosome rearrangement (CCR) involving chromosomes 2, 13, and 20 was ascertained in a normal female through the diagnosis of a deletion of 13q in her daughter. The child has mild clinical features and developmental delay consistent with proximal deletions of 13q that do not extend into band q32 and a del(13)(q12q14.1) that does not involve the retinoblastoma locus by FISH. Maternal studies by GTG banding and FISH showed a complex karyotype with bands 13q12.3→13q12.1::20p13 translocated to 2p13 and bands 2pter→2p13::13q12.3→13q14.1 translocated into band 20p13. This would be the first report of an interstitial deletion of 13q inherited from a parental complex chromosome rearrangement. © 2001 Wiley‐Liss, Inc.     

Duplication 9q34→qter identified by chromosome painting

We have studied an infant with multiple anomalies and a 46,XY,12p+ karyotype. Parental chromosomes were normal, and it was not possible to determine the identity of the extra material on chromosome 12 cytogenetically. Chromosome painting with probes from a chromosome 9 library identified this material as coming from chromosome 9, and cytogenetics established the duplication as 9q34→qter. Comparison of this patient with others reported with partial dup(9q) documented excellent concordance of minor anomalies, most notably dolichocephaly, “;deep-set”; eyes, short horizontal palpebral fissures, beaked nose, micrognathia, arachnodactyly, and developmental delay. Identification of cytogenetically indeterminate abnormalities by molecular cytogenetics is very important, as it permits prognosis to be offered for families of newborn infants with unbalanced karyo-types. © 1993 Wiley-Liss, Inc.     

Translocation 9q/13q resulting in duplication (trisomy 9pter→9q22) and deficiency (monosomy 13pter→13q12)

A profoundly retarded, 12-year-old female is described. Her phenotype is compatible with the clinical features of the trisomy 9p syndrome. Cytogenetic analyses showed her to be trisomic for 9pter→9q22 and monosomic for 13pter→13q12, as the result of adjacent-2 segregation during meiosis in her mother. The family pedigree shows this (9;13) translocation to be present in at least three generations.     

New case of mosaic tetrasomy 9p with additional neurometabolic findings

Tetrasomy 9p is a rare chromosomal aberration that was described in 28 previous patients. Here we report on a newborn girl who was referred for genetic evaluation because of developmental delay, hypertonicity, microcephaly, minor anomalies, and neurometabolic findings. She had an isochromosome 9p (pter → p10 → pter) in 32% of blood cells. The extra chromosome was not found in amniocytes. Examination of fibroblasts from different skin biopsies also showed mosaicism in this tissue. In a first biopsy from the abdominal wall, the cells (n = 50) had a normal chromosomal complement. Further analysis of fibroblasts from the left forearm showed the isochromosome 9p in 5 out of 8 mitoses. Fluorescence in situ hybridization (FISH), using a whole chromosome 9 probe, confirmed that the extra marker was 9 in origin. Molecular studies showed that the isochromosome was of maternal origin. Meiotic nondisjunction was followed by centromeric misdivision and postzygotic loss of the marker. Am. J. Med. Genet. 75:530–533, 1998. © 1998 Wiley-Liss, Inc.     

Partial duplication of 3q (q25.1→q26.1) without the Brachmann-de Lange phenotype

Partial duplications of chromosome 3 have previously been reported to have phenotypic characteristics similar to Brachmann-de Lange syndrome (BDLS). We present the case of a 13-Year-old girl with an apparent duplication in the 3q25.1→q26.1 region but none of the manifestations commonly seen in BDLS. The chromosome 3 duplication was confirmed with a FISH painting probe of the involved region. These results suggest that the region critical for Brachmann-de Lange syndrome is not within the duplicated region of 3q25.1→q26.1. © 1993 Wiley-Liss, Inc.     

Balanced complex rearrangement involving chromosomes 8, 9, and 12 in a normal mother,derivative chromosome 9 with recombinant chromosome 12 in her daughter with minor anomalies

We report on a 19-month-old girl with a derivative chromosome 9 and a recombinant chromosome 12 resulting from a maternal balanced complex rearrangement involving chromosomes 8, 9, and 12. The karyotype of the phenotypically normal mother was 46,XX,t(8;12) (9;12) (8qter→8p23::12q12→12q15::9q32→9qter;9pter→9q32::12q15→12qter;12pter→12q12::8p23→8pter). The child's karyotype was 46,XX,?9,?12, +der(9) (9pter→9q32::12q15→12qter),+rec(12) (12pter→12q15::9q32→9qter) mat. The child had severe growth retardation, minor anomalies including trigonocephaly, hypertelorism, broad nasal root, apparently low-set and posteriorly angulated ears, triangular face, pectus carinatum, clinodactyly of fifth fingers, and almost normal psychomotor development. To the best of our knowledge, there have been only 3 previous reports of recombination derived from parental complex chromosome rearrangements. In the recombination products, the chromosomes were apparently balanced and the offspring had no clinical abnormalities. The present case exhibited abnormalities and may have a submicroscopic aberration of 12q arising from crossing over during maternal meiotic pairing, although her chromosomes appeared to be balanced. © 1993 Wiley-Liss, Inc.     

Partial trisomy 3q syndrome inherited from familial t(3;9)(q26.1; p23)

A five-year-old girl was referred to prometaphase chromosome analysis because of mental retardation, facial dysmorphic features suggestive of Cornelia de Lange syndrome, cleft palate and additional minor congenital malformations of the cardiac system and fingers and toes. A familial balanced translocation (3;9)(q26.1; p23) was found. The karyotype of the proposita was 46,XX,der(9),t(3;9)(q26.1;p23). Thus the patient was trisomic for 3q26.1-qter and monosomic for 9p23-pter. The unbalanced chromosome constitution was not detected by standard Q-banding analysis shortly after birth. The karyotype was misdiagnosed as 46,XX,9(p+) in the proposita and her mother, and thought to be a normal variant of chromosome 9. The repeated cytogenetic study led to the diagnosis of the translocation and to the possibility of prenatal diagnosis in the translocation carriers. A survey of 22 published cases of dup(3q) showed that nearly 60% were secondary to familial balanced rearrangements with an excess of maternally derived abnormal chromosomes 3. Red blood cell galactose-1-phosphate-uridyltransferase (GALT) activity was normal in the patient, consistent with previous assignment of the gene locus for GALT to 9p13 (Shih et al. 1982).     

Malformation syndrome of duplication 12q24.1→qter

While duplication and deletion of the short arm of chromosome 12 cause well-recognized syndromes, duplication of the long arm of chromosome 12 is rarely observed. We are reporting a duplication of chromosome 12 distal to band q24.1 in a five-month-old child. His chromosome constitution is 46,XY,-4, + der(4),t(4:12)(p16;q24.1)mat. The balanced translocation is also carried by his maternal grandmother and two of the mother's brothers. The malformation syndrome consisted of unusual facial appearance and anomalies of the musculoskeletal, cardiovascular, genitourinary, and central nervous systems. Four previously reported patients had similar break points on chromosome 12 with similar malformations; therefore, phenotype-karyotype correlation suggests a definitive malformation syndrome associated with duplication of chromosome region 12q24.1→qter.     

Tetrasomy 15q25.3 → qter resulting from an analphoid supernumerary marker chromosome in a patient with multiple anomalies and bilateral Wilms tumors

We describe a girl who had been followed since birth for apparent Shprintzen‐Goldberg syndrome (SGS), with macrosomia, long fingers and toes, and craniosynostosis, and presented at 4 years of age with bilateral Wilms tumors (also called nephroblastoma). Cytogenetic analysis of her peripheral blood revealed a de novo supernumerary marker chromosome. This stable marker chromosome is present in 19 of 20 lymphocytes analyzed, as well as in all 40 tumor cells (20 from each tumor) studied. Classical and molecular cytogenetic studies indicate that the marker is derived from an inverted duplication of chromosome 15q25.3 → qter and contains a neocentromere. The presence of this marker chromosome in our patient results in tetrasomy 15q25.3 → qter. The relationship between her genotype and phenotype are discussed in light of genes, including IGF1R and FES, mapped to the aneusomic segment. © 2002 Wiley‐Liss, Inc.     

Tetrasomy 15q25→qter: Cytogenetic and molecular characterization of an analphoid supernumerary marker chromosome

Tetrasomy for the distal long arm of chromosome 15 is a rare finding. It has been previously described in seven patients, all of whom had a supernumerary marker chromosome (SMC) derived from distal 15q. These SMC contained no apparent centromeres (C‐band/α‐satellite negative), and belong to a novel class of SMC with neocentromeres. We present the oldest surviving patient with tetrasomy for distal 15q. The proposita was a 10‐year‐old girl with moderate to severe mental retardation, absent speech, hypotonia, minor facial anomalies, unusual digits, and pigmentation anomalies. Mosaicism for a symmetrical SMC was identified in metaphases from lymphocytes and fibroblasts. Parental karyotypes were normal, indicating a de novo origin for the SMC. FISH with a whole chromosome paint for chromosome 15 showed that the SMC was derived entirely from chromosome 15. However, C‐banding and FISH with chromosome 15 probes D15Z1, D15S11, SNRPN, and PML were all negative. FISH with the FES probe at 15q26 showed hybridization to both ends of the SMC. The marker was interpreted as an analphoid inverted duplication of 15q25→qter containing a presumed neocentromere. Previous molecular studies suggested either a mitotic or paternal meiotic origin for these distal 15q SMC. However, molecular analysis with chromosome 15 polymorphic markers showed that the analphoid SMC(15) in the proposita originated from a maternal meiotic error. The origins and mechanisms involved in formation of these distal 15q SMC appear to be more diverse than for the proximal pseudodicentic SMC(15). Am. J. Med. Genet. 94:393–398, 2000. © 2000 Wiley‐Liss, Inc.     

The origin of trisomy 13

Trisomy 13 is one of the most common trisomies in clinically recognized pregnancies and one of the few trisomies identified in liveborns, yet relatively little is known about the errors that lead to trisomy 13. Accordingly, we initiated studies to investigate the origin of the extra chromosome in 78 cases of trisomy 13. Our results indicate that the majority of cases (>91%) are maternal in origin and, similar to other autosomal trisomies, the extra chromosome is typically due to errors in meiosis I. Surprisingly, however, a large number of errors also occur during maternal meiosis II ( approximately 37%), distinguishing trisomy 13 from other acrocentric and most nonacrocentric chromosomes. As with other trisomies, failure to recombine is an important contributor to nondisjunction of chromosome 13.     

20‐Mb duplication of chromosome 9p in a girl with minimal physical findings and normal IQ: Narrowing of the 9p duplication critical region to 6 Mb

We studied the case of a girl with a partial 9p duplication, dup(9)(p22.1 → p13.1). Molecular cytogenetics studies defined the chromosome 9 rearrangement as a direct duplication of 20 Mb from D9S1213 to D9S52. Microsatellite analysis demonstrated the presence of a double dosage of the paternal alleles and demonstrated that the duplication occurred between sister chromatids. The patient's phenotype was almost normal, with a few minor anomalies (dolichocephaly, crowded teeth, high arched palate) and normal IQ. The breakpoint's location in this patient and previously reported cases suggest that the critical region for the 9p duplication syndrome lies within a 6‐Mb portion of chromosome 9p22 between markers D9S267 and D9S1213. © 2002 Wiley‐Liss, Inc.