Adjacent-2 disjunction of a maternal t(9;22) leading to duplication 9pter→q22 and deficiency of 22pter→q11.2

The proposita presented at birth with multiple congenital anomalies including craniofacial anomalies, bilateral cleft lip and palate, abnormalities of the urogenital system, talipes equinovarus, and the DiGeorge sequence. Cytogenetic investigation showed a 46,XX,- 22,+der(9)t(9;22)(q22;q11.2) karyotype. The mother, maternal uncle, and maternal grandmother of the infant are carriers of a reciprocal balanced translocation involving chromosomes 9 and 22 at regions q22 and q11.2, respectively. The unbalanced karyotype seen in the proposita arose due to an adjacent-2 disjunction of the quadrivalent in the mother. Prenatal diagnosis of the second pregnancy of this woman showed a similar karyotype. Review of the literature shows that adjacent-2 disjunction may occur preferentially when certain chromosomes are involved in translocations.     

Partial 3p trisomy and different rearrangements involving chromosome 3 in the proposita's family

A case of partial 3p trisomy is reported here. A review of published cases (8 ♂, 2 ♀, 7 families) shows a characteristic pattern of anomalies, constituting one more syndrome of multiple congenital anomaly and mental retardation (MCA/MR) characterized by microcephaly, brachycephaly, frontal bossing, temporal indentation, square face, hypertelorism or telecanthus, epicanthus, short nose with a large tip, prominent cheeks, long and protruding philtrum, large and downturned mouth, protruding mid-upper lip, micro- or retrognathia, short neck, congenital heart defects, gastrointestinal malformation, penile hypoplasia, neuromotor or mental retardation, and predominance of whorls on digits. The proposita had a 46,XX,der(11),t(3;11)(p21;q25) karyotype. The mother was a carrier of a de novo 3;11 balanced translocation. Chromosome mosaicism was detected in a female sibling of the proposita: 46% of her cells were 46,XX and 54% had a 46,XX,t(3;20)(p21;q13) karyotype - ie, a de novo 3;20 balanced translocation. We discuss the origin of this mosaicism and the possible meaning of the breaks involving the same region of chromosome 3 (region 3p21) in the members of the proposita's family.     

A balanced translocation t(4;9) (q35;q12) with a breakpoint within the heterochromatic region of chromosome 9 in a woman with recurrent abortion

A case of recurrent abortion was found to be associated with the presence in the mother of a balanced translocation between chromosomes 4 and 9. The karyotype of the proposita was: 46, XX, t(4;9)(q35;q12). The effects of this translocation are discussed in the light of other cases reported in the literature.     

Familial complex chromosome rearrangement giving rise to balanced and unbalanced recombination products

We report on a family ascertained through a 14-month-old girl with a terminal deletion of chromosome 8p23.1. Analysis of the karyotype of other relatives showed that the mother is the carrier of a balanced complex 4-break chromosome rearrangement, which she and her brother inherited from their father following recombination. This complex chromosome rearrangement (CCR) was confirmed by fluorescence in-situ hybridization (FISH) using libraries for chromosomes 1, 8, and 9, and telomeric probes for the long arm of chromosome 9. The karyotype of the maternal grandfather was 46,XY,t(1;8) (p31;q21.1),t(8;9)(p23.1;q34). The karyotype of his daughter is 46,XX,rec(8)t(1;8) (p31;q21.1)t(8;9)(p23.1;q34)pat. The karyotype of the proposita is 46,XX,rec(8)t(8;9) (p23.1;q34)mat, and that of her abnormal elder sister is 46,XX,t(1;8)(p31;q21.1)rec(8) t(8;9)(p23.1;q34)mat,der(9)t(8;9)(p23.1;q34) mat. Unbalanced segregation and/or recombination during maternal meiosis gave rise to the two abnormal sisters, one effectively with 8p trisomy and the other with monosomy for that same 8p segment. To our knowledge, this is the first case of a familial CCR giving rise to unbalanced recombination products. Am. J. Med. Genet. 79:30–34, 1998. © 1998 Wiley-Liss, Inc.     

Segregating Reciprocal (4;21) (q21;q21) Translocation with Proposita Trisomic for Parts of 4q and 21

The segregation of a balanced reciprocal (4;21)(q21;q21) translocation is described. The family was ascertained through a clinically abnormal proposita with an unbalanced karyotype 47,XX,+der(21),t(4;21)(q21;q21)mat. The proposita was trisomic for regions 4q2, 4q3, 21p, and 21q1. Symptoms that might be attributed to the partial trisomy for parts of 4q were narrow bird face with slanting forehead, prominent nasal bridge and small mandible, downward pointing corners of the mouth, deformed ears, palpebral ptosis, and bushy eyebrows. Similar symptoms occur in other trisomy and deletion syndromes.     

Trisomy 16pter to 16q12.1 and monosomy 22pter to 22q11.2 resulting from adjacent-2 segregation of a maternal complex chromosome rearrangement

We report on a 16-week-old male fetus with partial trisomy 16 and partial monosomy 22 resulting from 3:3 adjacent-2 segregation of a maternal balanced complex chromosome translocation involving chromosomes 5, 16, and 22. The karyotype of the 29-year-old phenotypically normal mother was 46,XX,t(5;16;22)(q31.3;q12.1;q11.2). The karyotype of the fetus was 46,XY,der(5)t(5;16;22)(q31.3;q12.1;q11.2),+der(16)t(5;16;22)mat,−22. The fetus had multiple congenital anomalies, including bilateral cleft lip and palate. Am. J. Med. Genet. 73:327–329, 1997. © 1997 Wiley-Liss, Inc.     

Familial reciprocal translocation, t(2;10)(p24;q26), resulting in duplication 2p and deletion 10q

We describe a familial reciprocal translocation between the distal part of the short arm of chromosome 2 and the long arm of chromosome 10. Five individuals in two generations had multiple congenital anomalies. Their karyotypes were 46, XX or XY,−10, + der(10), t(2;10)(p24;q26). Seven persons were balanced translocation carriers whose karyotypes were 46, XX or XY, t(2;10)(p24;q26). Common manifestations included mental retardation, strabismus, narrow high-arched palate, wide alveolar ridges, other facial abnormalities, genital abnormalities and mutism. The phenotype of the unbalanced individuals is compared to that of previously published cases of the syndrome of partial duplication 2p and to reported patients with partial deletion of 10q.     

An unbalanced autosomal translocation (7;9) associated with feminization

A newborn girl presented with generalized mild dysmorphic features. She later developed heart failure and hydrocephalus, and died aged 5 months. Chromosome analysis revealed an unbalanced reciprocal translocation (with partial trisomy for half of the long arm of 7 and partial monosomy for the short arm of chromosome 9) and normal but inappropriate sex chromosomes (XY). The karyotype (46,XY,-9, +der(9),t(7;9)(q31.1;p23)pat) was inferred from her father who was a balanced carrier: 46, XY,(7;9)(q31.1;p23). The evidence of the present case, when considered with that of previous reports, suggests that deletion of genes on the 9p may have caused the feminization and therefore that the 9p region may contain genes which are important in the normal process of testis formation.     

Duplication and deletion of chromosome band 2(p21p22) resulting from a familial interstitial insertion (2;11)(p21;p15)

Routine amniocentesis for advanced maternal age led to the prenatal diagnosis of a fetus with a karyotype of a 46,XX,del(2)(p21p22). At delivery the baby had holoprosencephaly as the major clinical finding, which has been associated with a deletion of band 2p21 in several other case reports. Chromosome studies of the parents showed a normal 46,XY karyotype in the father, and a balanced interstitial insertion 46,XX dir ins (11;2)(p15.1;p21p22) in the mother. Subsequent chromosome studies of other relatives documented a 23-year-old half-brother of the proposita with a partial trisomy for the segment deleted in the proposita. The half-brother showed the derivative chromosome 11 from the mother, resulting in a 46,XY,der(11)dup(2)(p21p22) karyotype. Major clinical findings include short stature, mild development delay, and behavior abnormalities. A half-sister of the proposita is also a balanced carrier of the dir ins (11;2) (p15.1;p21p22.2). The association of the deletion chromosome band 2p21 and the clinical finding of holoprosencephaly is further supported by the findings in this family. © 1994 Wiley-Liss, Inc.     

Partial trisomy 12q.

A partial trisomy 12q243 leads to qter resulting from a maternal balanced translocation, 46,XX,t(9;12)(p243;q243) was detected in a male newborn with multiple congenital abnormalities. The maternal grandmother was also a carrier of the 9;12 translocation. Our patient exhibited a number of clinica features similar to two others reported, who were also trisomic for the distal part of 12q. Aberrations of chromosome 12 are very rare. There have been only two reports of partial trisomy 12q, both the result of a familial translocation. We describe a third unbalanced case.     

Mental retardation with 45 chromosomes 45,XX,--5,--14,+der(5) t(5,14)(p15;q13) mat due to familial balanced reciprocal translocation.

A girl with severe mental retardation and odd facies and some features of the cri-duchat syndrome was found to have only 45 chromosomes. Her karyotype was 45,XX, -5, -14,+der(5) t(5,14)(p15;q13) mat. Her mother and her two sisters were found to be balanced reciprocal translocation carriers having 46 chromosomes, one of which was a very small (14pter leads to 14q13::5p15leads to 5pter) that was missing in the proposita.     

Trisomy 9q3 syndrome: a case report and review of the literature

A girl with partial trisomy 9q is reported. She was characterized by dolichomorphism, abnormalities of the digits, a cardiac defect and craniofacial dysmorphism. A high-resolution analysis revealed the karyotype to be: 46,XX,-3,+ der(3)t(3;9)(q29;q13) de novo. A phenotype-karyotype correlation study in 22 cases of partial trisomies 9q supported the delineation of a trisomy 9q3 syndrome. The smallest region of overlap was confined to 9q32.     

Mosaicism for trisomy 3q arising from an unbalanced, de novo t(3;15).

We report on a 2 1/2 year old girl who is dysmorphic, developmentally delayed, and mosaic for an unbalanced, de novo translocation between chromosomes 3 and 15. The karyotype from peripheral blood lymphocytes is 46,XX (50) and the karyotype from skin fibroblasts is 46,XX (28)/46,XX,der(15)t(3;15)(q11;p11) (23). The mechanism for the generation of this unbalanced, de novo translocation is discussed.     

两例分别由父源性平衡易位和母源性插入易位导致8p部分三体智力低下患儿的临床表型和遗传学分析

目的 明确两例智力低下患儿8号染色体短臂异常性质和来源,分析其染色体改变与表型的相关性.方法 首先应用常规G显带分析2例患儿及父母外周血染色体改变,然后应用比较基因组杂交芯片(array comparative genomic hybridization,array CGH)对其中1例常规核型分析的结果进行精确定位.结果 例1母亲的染色体改变为8p和3q的平衡插入易位,该患儿继承了母亲的1条衍生3号染色体,核型为46,XX,der(3) inv ins (3;8)(q25.3;p23.1p11.2)mat,导致8p部分三体.Array CGH分析显示重复区域为8p11.21-8p22,片段大小为26.9 Mb,该患儿主要表现为智力低下,未见其他8p三体的典型临床特征.例2父亲的核型为8p和11q的平衡易位,该患儿继承了父亲的1条衍生11号染色体,核型为46,XX,der(11)t(8;11)(p11.2;q25)pat,临床表现为智力低下,特殊面容,同时伴有先天性心脏病和骨骼异常,与典型8p三体表型相似,但面容特征不典型.结论 8p部分三体是2例患儿异常表型的主要原因,但与典型的8p三体相比,表型存在异质性;父母染色体分析可以帮助明确易位的性质从而有利于再发风险评估;与传统的细胞遗传学分析方法相比,arrayCGH在染色体异常分析中具有更高的分辨率和准确性.

Abstract：

Objective To determine the origin of aberrant chromosomes involving the short arm of chromosome 8 in two mentally retarded children, and to correlate the karyotype with abnormal phenotype. Methods Routine G-banding was performed to analyze the karyotypes of the two patients and their parents, and array comparative genomic hybridization (array CGH) was used for the first patient for fine mapping of the aberrant region. Results The first patient presented with only mental retardation. The father had normal karyotype. The mother had an apparent insertion translocation involving chromosomes 8 and 3 [46,XX, inv ins (3;8) (q25.3;p23.1p11.2)], the karyotype of the child was ascertained as 46,XX,der(3) inv ins (3;8)(q25.3;p23.1p11.2). Array CGH finely mapped the duplication to 8p11.21-8p22, a 26.9Mb region. The other patient presented with mental retardation, craniofacial defects, congenital heart disease and minor skeletal abnormality. The mother had normal karyotype. The father had an apparently balanced translocation involving chromosome 8p and 11q, the karyotype was 46,XY, t(8;11)(p11.2;q25). The karyotype of the child was then ascertained as 46,XX,der(11)t(8;11)(p11.2;q25). Conclusion These results suggested that partial trisomy 8p was primary cause for the phenotypic abnormalities of the two patients, whereas a mild phenotypic effect was observed in patient 1. Parental karyotype analysis could help define the aberrant type and recurrent risk evaluation. In contract to routine karyotype analysis, aberrant regions could be mapped by array CGH with higher resolution and accuracy.     

Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly

Chromosome aberrations, mendelian mutations and exogenous agents can cause holoprosencephaly. Therefore, etiologic evaluation of holoprosencephaly is necessary for obstetricians and genetic counselors, once a prenatal diagnosis of holoprosencephaly has been made. We present four pregnancies in three women in which routine sonographic examinations led to the prenatal diagnosis of holoprosencephaly. Prenatal cytogenetic analysis and fluorescence in situ hybridization demonstrated a 46, XY, del(7)(pter→q32:) and a 46, XY, der(2)t(2;3)(q37;p21)pat karyotype respectively in two fetuses with cyclopia, and a 46, XX, der(2)t(2;3)(q37;p21)pat and a 46, XX, der(7)t(3;7)(p23;q36) karyotype respectively in two fetuses with premaxillary agenesis. In conclusion, terminal deletion 7q and partial trisomy 3p in holoprosencephalic fetuses indicates that genes contributing to craniofacial development reside in these critical regions. Proper prognostic evaluation in further pregnancies requires expertise in cytogenetics and genetic counseling.     

Three cases of partial trisomy 9q in one generation due to maternal reciprocal t(6;8;9) translocation

A family is described in which three siblings had congenital abnormalities consistent with partial trisomy 9q syndrome. Karyotyping indicated that the mother was a carrier of two separate balanced reciprocal translocations involving three chromosomes (46,XX,t (6;8;9)(6q27;8p23;9q32;9q13] resulting from four breakpoints. The three siblings had inherited the der(8) from their mother and hence were partially trisomic for 9q32----9qter and partially monosomic for 8p23----8pter (46,XX,der(8),t(8;9)(p23;q32)mat). The clinical features of the three cases were comparable to those reported in the literature.     

Analysis of a familial three way translocation involving chromosomes 3q, 6q, and 15q by high resolution banding and fluorescent in situ hybridisation (FISH) shows two different unbalanced karyotypes in sibs.

We report on a familial three way translocation involving chromosomes 3, 6, and 15 identified by prometaphase banding and fluorescence in situ hybridisation (FISH). Two mentally retarded sibs with different phenotypic abnormalities, their phenotypically normal sister and mother, and two fetuses of the phenotypically normal sister were analysed. The terminal regions of chromosomes 3q, 6q, and 15q were involved in a reciprocal translocation, in addition to a paracentric inversion of the derivative chromosome 15. Conventional cytogenetic studies with high resolution GTG banding did not resolve this rearrangement. FISH using whole chromosome paints (WCPs) identified the chromosomal regions involved, except the aberrant region of 3q, which was undetectable with these probes. Investigation of this region with the subtelomeric FISH probe D3S1445/D3S1446 showed a balanced karyotype, 46,XX,t(3;15;6) (q29;q26.1;q26), inv der(15) (q15.1q26.1) in two adult females and one fetus. It was unbalanced in two sibs, showing two different types of unbalanced translocation resulting in partial trisomy 3q in combination with partial monosomy 6q in one patient and partial trisomy 15q with partial monosomy 6q in the other patient and one fetus. These represent apparently new chromosomal phenotypes.     

De novo simultaneous reciprocal translocation and deletion.

A female infant with severe mental retardation, general hypotonicity, and a history of generalised oedema, cyanosis, heart murmur, and nystagmus in the first days of life was found to have both a translocation and a deletion. Her karyotype was 46,XX,del(21)t(18;21)(18p ter leads to 18q11::21q21 leads to 21qter;21pter leads to 21q11::18q11 leads to 18q ter). The karyotype of both parents was normal. The proposita is the result of a three break point exchange and is monosomic for part of the dark band q11 q21 of chromosome 21. It is suggested that in cases with mental retardation and apparent balanced de novo reciprocal translocation a small undetected deletion in one of the chromosomes involved in the translocation could explain the mental retardation.