Monosomy and trisomy of 15q24→qter in a family with a translocation t(6;15)(P25;q24)

A child with multiple anomalies, including growth retardation, a left-sided diaphragmatic hernia with lung hypoplasia, and cerebral malformations is described. Cytogenetic investigation demonstrated a deletion of the distal part of one chromosome 15, del(15)(q24qter), an aberration not previously described. Family studies revealed that the mother had a balanced translocation, t(6;15)(p25;q24). Two of her subsequent pregnancies resulted in abortions after prenatal diagnosis: one fetus was trisomic for 15q24→qter, while the other had monosomy 15q24→qter and a left-sided diaphragmatic hernia similar to the first child.     

X;14 translocation: An exception to the critical region hypothesis on the human X-chromosome

We report on a family in which an X;14 translocation has been identified. A phenotypically normal female, carrier of an apparently balanced X-autosome translocation t(X;14) (q22;q24.3) in all her cells and a small interstitial deletion of band 15q 112 in some of her cells had 2 offspring. She represents a fifth case of balanced X-autosome translocation with the break point inside the postulated critical region of Xq(q13 q26) associated with fertility. The break point in this case is located in Xq22, the same band as in four previously published exceptional cases. In most of her cells, the normal X was inactivated. Her daughter, the proposita, has an unbalanced karyotype 46,X,der(X), t(X;14)(q22;q24.3)mat, del(15)(q11.1q11.3)mat. She is mildly retarded and has some Prader-Willi syndrome manifestations. She has two normal 14 chromosomes, der(X), and deletion 15q11.2. Her clinical abnormalities probably could be attributed to the deletions 15q and Xq rather than 14q duplication. In most of cells, der(X) was inactivated. We assume that spreading of inactivation was extended to the 14q segment on the derivative X. Late replication and gene dose studies support this view. Another daughter, who inherited the balanced X;14 translocation and not deletion 15 chromosome, is phenotypically normal.     

Robertsonian (15q;15q) translocation in a child with Angelman syndrome: Evidence of uniparental disomy

A balanced Robertsonian translocation 45,XY,t(15q15q) was detected in a patient with mental retardation, microcephaly, and hypertonia. Deletion of the 15q11q13 region was unlikely based on fluorescence in situ hybridization studies that revealed hybridization of appropriate DNA probes to both arms of the Robertsonian chromosome. Inheritance of alleles from 13 highly polymorphic DNA markers on chromosome 15 showed paternal uniparental isodisomy. The clinical, cytogenetic, and molecular results are consistent with a diagnosis of Angelman syndrome. © 1996 Wiley-Liss, Inc.     

A de novo translocation, 14q21q, with a microchromosome-14p21p

A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11;p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed.     

A de novo translocation, 14q21q,with a microchromosome—14p21p

A familial translocation, t(14;21)(14p21p;14q21q), in a mother and her child is described. The translocation was ascertained through the birth of a Down syndrome baby with the chromosome constitution 47,XX,-14, +der 14, +der 21,t(14;21)(q11; p12) mat. A 1:3 segregation in the maternal meiosis is suggested for the evolution of the unbalanced chromosome state. The main translocated chromosome 14q21q mimics the product of a Robertsonian translocation, while the 14p21p chromosome has the morphology of a satellited microchromosome. The cytogenetic nature of this translocation is discussed.     

Prader-Willi syndrome and Robertsonian translocations involving chromosome 15

A case of Prader-Willi syndrome is presented in which high resolution chromosome analysis revealed not only a familial Robertsonian translocation [t(13q15q)], but also a del(15) (q11.2q13) of the chromosome 15 not involved in the translocation. While there have been numerous reports of Robertsonian translocations involving chromosome 15 in patients with Prader-Willi syndrome, in this case, the Robertsonian translocation was shown to be unrelated to the clinical findings.     

Unusual clinical features in an Angelman syndrome patient with uniparental disomy due to a translocation 15q15q

We had previously described a patient with an overgrowth syndrome and the chromosome constitution 45,XY,t(15q15q) (Wajntal et al., DNA Cell Biol 1993: 12: 227–231). Clinical reassessment and the use of molecular studies, including methylation analysis with an SNRPN probe, microsatellite analyses of D15S11 , GABRB3 and D15S113 loci, and fluorescence in situ hybridization (FISH) using the SNRPN and GABRB3 probes, are consistent with a diagnosis of Angelman syndrome (AS) due to paternal isodisomy. This is the fourth report case of a translocation 15q15q with paternal uniparental disomy (UPD). Our findings suggest that some patients with clinical features of AS have hyperphagia and obesity with overgrowth, and that these features should not rule out a diagnosis of AS.     

Paternal uniparental disomy in a child with a balanced 15;15 translocation and Angelman syndrome

Chromosome 15 (15q11-q13) abnormalities cause two distinct conditions, Angelman syndrome (AS) and Prader-Willi syndrome (PWS). We present the first case of a child with a balanced 15;15 translocation and AS in whom molecular studies were crucial in confirming a diagnosis. DNA polymorphisms demonstrated paternal uniparental disomy for chromosome 15, consistent with the diagnosis of AS. The molecular studies also showed the patient to be homozygous at all loci for which the father was heterozygous, suggesting that the structural rearrangement was an isochromosome 15q and not a Robertsonian translocation. © 1993 Wiley-Liss, Inc.     

Acquired Robertsonian translocations in two leukemia patients.

Robertsonian translocations were observed in two leukemia patients. The first case was a patient with chronic lymphocytic leukemia, who was found to have a rare Robertsonian translocation der(14;15)(q10;q10). The second case, a patient with acute myeloid leukemia, had multiple Robertsonian translocations: der(15)t(13;15)(q11.1;p11.1), der(14;22)(q10;q10), and dic(21;22)(p11.1;p11.1). Acquired multiple Robertsonian translocations have not been reported previously in leukemia.     

Two cases of Robertsonian translocations in oligozoospermic males and their consequences for pregnancies induced by intracytoplasmic sperm injection

Two case histories are presented documenting structural chromosome abnormalities in infertile males. The abnormalities were detected only after application of intracytoplasmic sperm injection (ICSI) was repeatedly unsuccessful or resulted in an abnormal pregnancy. A mosaic Robertsonian translocation 45,XY,der(13;13)(q10; q10)/46,XY,t(13;13)(p10;p10), der(13p;13p) incompatible with normal offspring was found in a male with extreme oligozoospermia after three subsequent ICSI treatments were unsuccessful and one had resulted in a spontaneous abortion. A second case involved a Robertsonian translocation 45,XY,der(13;14)(q10;q10) which was detected in a male with extreme oligozoospermia after ultrasound abnormalities were found in an ICSI-induced twin pregnancy. Amniocentesis showed an unbalanced 46,XY,+13,der(13;14)(q10;q10) karyotype in one twin and a Robertsonian 45,XX,der(13;14)(q10;q10) karyotype in the other twin. Chromosome analysis of males with abnormal sperm characteristics is advised prior to ICSI.      

一4q部分三体10q部分单体患儿的分子细胞遗传分析

目的 确定一生长迟缓、智力低下患儿的核型,分析其染色体变异与表型的相关性,同时探讨微阵列比较基因组杂交(array-based comparative genomic hybridization,array-CGH)在临床分子细胞遗传诊断中的应用及其优越性.方法 应用G显带染色体分析、array-CGH、荧光原位杂交(fluorescence in situ hybridization,FISH)和实时定量PCR(real-time quantitative PCR,RQ-PCR)对患儿及其亲属进行核型分析.结果 G显带染色体分析显示患儿存在1条来源于父亲的10号衍生染色体der(10)t(4;10)(q25;q26),其父亲和祖母均是t(4;10)(q25;q26)平衡易位携带者.Array-CGH显示患儿存在4q26-q35.2三体,并将断裂点定位于4q26,此外,还发现患儿10号染色体存在一约0.54 Mb的微缺失del(10)(q26.3).FISH和RQ-PCR证实父亲和祖母也存在del(10)(q26.3).结论 del(10)(q26.3)并不导致表型异常,患儿的异常表型可归因于4q26-q35.2三体.与传统的细胞遗传分析方法 相比,array-CGH具有高分辨率和高准确性等优点.     

Segregation of a familial balanced (12;10) insertion resulting in dup(10)(q21.2q22.1) and del(10)(q21.2q22.1) in first cousins

An interchromosomal insertion in 3 generations of a family was ascertained through two developmentally delayed first cousins. Cytogenetic analysis using G-banding and chromosome painting showed an apparently balanced direct insertion of chromosome 10 material into chromosome 12, ins(12;10)(q15;q21.2q22.1), in the mothers and grandfather of these children. The proposita inherited only the derivative 10 chromosome, resulting in deletion of 10q21.2 → 22.1 while her cousin inherited only the derivative 12, resulting in duplication of 10q21.2 → 22.1. A comparison of the proposita with published deletion cases suggests a pattern of anomalies attributable to deletion of the 10q21 → q22 region: developmental delay, hypotonia, a heart murmur, telecanthus, broad nasal root and ear abnormalities. This is the first report of a nontandem duplication of the 10q21 → q22 region. The phenotype of the cousin with the duplication does not overlap greatly with published tandem 10q duplications. Finally, this report reaffirms the importance of obtaining family studies of patients with interstitial chromosomal abnormalities. Am J. Med. Genet. 69:188–193, 1997. © 1997 Wiley-Liss, Inc.     

Minimal phenotype in a girl with trisomy 15q due to t(X;15)(q22.3;q11.2) translocation

Few cases of de novo unbalanced X;autosome translocations associated with a normal or mild dysmorphic phenotype have been described. We report a 3-year-old dizygotic female twin with prenatally ascertained increased nuchal translucency. Prenatal chromosome studies revealed nearly complete trisomy 15 due to a de novo unbalanced translocation t(X;15)(q22;q11.2) confirmed postnatally. A mild phenotype was observed with normal birth measurements, minor facial dysmorphic features (hypertelorism, short broad nose, and a relatively long philtrum), and moderate developmental delay at the age of 3 years in comparison to her male fraternal twin. Replication timing utilizing BrdU and acridine-orange staining showed that the der(X) chromosome was late-replicating with variable spreading of inactivation into the translocated 15q segment. The der(X) was determined to be of paternal origin by analyses of polymorphic markers and CGG-repeat at FMR1. Methylation analysis at the SNRPN locus and analysis of microsatellites on 15q revealed paternal isodisomy with double dosage for all markers and the unmethylated SNRPN gene. The Xq breakpoint was mapped within two overlapping BAC clones RP11-575K24 and RP13-483F6 at Xq22.3 and the 15q breakpoint to 15q11.2, within overlapping clones RP11-509A17 and RP11-382A4 that are all significantly enriched for LINE-1 elements (36.6%, 43.0%, 26.6%, 22.0%, respectively). We speculate that the attenuated phenotype may be due to inactivation spreading into 15q, potentially facilitated by the enrichment of LINE-1 elements at the breakpoints. In silico analysis of breakpoint regions revealed the presence of highly identical low-copy repeats (LCRs) at both breakpoints, potentially involved in generating the translocation.     

Two different structural abnormalities of chromosome 13 in offspring of chromo-somally normal parents with two fragile sites

Two siblings were found with different structural abnormalities involving their maternally inherited chromosome 13. The proband exhibited a ring 13 and a small fragment: 46, XX, r(13) (pllq34), +f, while her clinically normal brother carried a dicentric Robertsonian translocation: 45, XY, dic(13;15) (pl 1;pl 1). Both parents had normal karyotypes in peripheral blood and skin fibroblasts. The structural abnormalities of chromosome 13 may be due to an unstable gonadal 13; 15 translocation in the mother. In addition, two autosomal fragile sites were segregating in this family. The mother had a fragile (16) (q22) which was inherited by the proband. The father and paternal grandmother possessed a fragile (12)(q13) which was not inherited by either child. The expression of both fragile sites was dependent on culture conditions.     

Familial robertsonian translocation 15;21 and rare paracentric inv(21): unexpected re-inversion in a child with translocation trisomy 21

We present a family with a Robertsonian translocation (RT) 15;21 and an inv(21)(q21.1q22.1) which was ascertained after the birth of a child with Down syndrome. Karyotyping revealed a translocation trisomy 21 in the patient. The mother was a carrier of a paternally inherited RT 15;21. Additionally, she and her mother showed a rare paracentric inversion of chromosome 21 which could not be observed in the Down syndrome patient. Thus, we concluded that the two free chromosomes 21 in the patient were of paternal origin. Remarkably, short tandem repeat (STR) typing revealed that the proband showed one paternal allele but two maternal alleles, indicating a maternal origin of the supernumerary chromosome 21. Due to the fact that chromosome analysis showed structurally normal chromosomes 21, a re-inversion of the free maternally inherited chromosome 21 must have occurred. Re-inversion and meiotic segregation error may have been co-incidental but unrelated events. Alternatively, the inversion or RT could have predisposed to maternal non-disjunction.     

Inherited unbalanced subtelomeric translocation in a child with 8p- and Angelman syndromes

A 10 1/2-month-old boy was found to have an unbalanced karyotype, 45,XY,der(8)t(8;15) (p23.3;q13). One of 83 analyzed cells also contained an unidentified small marker. Fluorescence in situ hybridization (FISH) using cosmic probes for SNRPN, D15S10, and GABRB3 for the Prader-Willi syndrome (PWS)/Angelman syndrome (AS) critical region were not present on the derived chromosome. The child had some physical findings compatible with monosomy 8p. The mother also was a balanced carrier for the translocation. She also had 2/80 cells with an additional small marker chromosome, similar in size to the extra chromosome in the one cell of the propositus. FISH using an 8 paint did not show the reciprocal exchange on the der(15) but was demonstrated by using an 8p telomeric probe. At 18 months of age the child has some manifestations of AS. Earlier diagnosis may have been masked by the 8p- phenotype, or related to difficulty in diagnosing AS in infants. Am. J. Med. Genet. 70:150–154, 1997. © 1997 Wiley-Liss, Inc.     

一例1q部分三体4q部分单体导致Pierre Robin序列征的遗传学分析

目的对1例临床诊断为Pierre Robin序列征的患儿进行细胞及分子遗传学分析,寻找遗传学病因。方法应用外周血染色体核型分析、核苷酸多态性微阵列检测和荧光原位杂交技术,分别对1例表型为下颌小、舌后坠、上呼吸道阻塞、上颚裂开、颈短的患儿及其正常表型的父母进行检测。结果患儿核型为46,XY,der(4)add(4)(q34);母亲核型为46,XX,t(1;4)(q43;q34);父亲核型为46,XY。患儿芯片检测结果为arr[hg19]1q42.2q44(232527958-249202755)×3,4q34.3q35.2(168236901-190880409)×1;父母芯片检测结果正常。母亲荧光原位杂交检测结果为ish t(1;4)(q42;34)。母亲为平衡易位携带者;患儿的4号衍生染色体来源于母亲其中一条结构重排的4号染色体,导致1q42.2q44片段三体、4q34.3q35.2片段单体。结论患儿的1号染色体片段重复及4号染色体片段缺失可能导致其Pierre Robin序列征相关表型。     

A case of Prader – Willi syndrome arising as a result of familial unbalanced translocation t(11;15)(q25;q13)

We report on a case of Prader-Willi syndrome (PWS) with a true reciprocal unbalanced translocation, 45,XX,-15,der(11)t(11;15)pat. The proposita was diagnosed clinically as having severe PWS. Molecular studies revealed loss of the paternal methylation pattern at locus D15S63 and a deletion encompassing the loci from at least D15S10 to D15S97 of paternal chromosome 15. FISH studies confirmed the deletion of 15q11-q13 region and the presence of two telomeres on all chromosomes. The proposita's father, the father's sister and their mother are all carriers of the same balanced translocation t(11;15)(q25;q13). By genomic imprinting we would expect that if the father's sister were to give birth to a child with the same unbalanced translocation as the proband, it would be affected by Angelman syndrome.
To date, a similar familial unbalanced translocation due to loss of the small chromosome 15 derivative has not been described.     

X;14 translocation:an exception to the critical region hypothesis on the human X-chromosome

We report on a family in which an X;14 translocation has been identified. A phenotypically normal female, carrier of an apparently balanced X-autosome translocation t(X;14)(q22;q24.3) in all her cells and a small interstitial deletion of band 15q112 in some of her cells had 2 offspring. She represents a fifth case of balanced X-autosome translocation with the break point inside the postulated critical region of Xq(q13 q26) associated with fertility. The break point in this case is located in Xq22, the same band as in four previously published exceptional cases. In most of her cells, the normal X was inactivated. Her daughter, the proposita, has an unbalanced karyotype 46,X,der(X), t(X;14)(q22;q24.3)mat, del(15)(q11.1q11.3)mat. She is mildly retarded and has some Prader-Willi syndrome manifestations. She has two normal 14 chromosomes, der(X), and deletion 15q11.2. Her clinical abnormalities probably could be attributed to the deletions 15q and Xq rather than 14q duplication. In most of cells, der(X) was inactivated. We assume that spreading of inactivation was extended to the 14q segment on the derivative X. Late replication and gene dose studies support this view. Another daughter, who inherited the balanced X;14 translocation and not deletion 15 chromosome, is phenotypically normal.