Novel chromosomal translocation t(11;9)(p15;p23) involving deletion and duplication of 9p in a girl associated with autism and mental retardation

We describe a 5-year-old girl presented with autism and mental retardation features. Conventional karyotyping revealed a novel unidirectional translocation t(11;9)(p15;p23). HumanCytoSNP-12 Chip analysis identified a 13 Mb deletion from 9p24.3 to 9p23 and a 12.5Mb duplication from 9p23 to 9p21.2. The karyotype was described as 45,XX,psu dic(11; 9)(p15;p23), which was reported for the first time here. The deleted region, extending from 9p24.3 to 9p23, overlaps with the candidate region for monosomy 9p syndrome and contains a potential autism spectrum disorders (ASD) locus. The duplication region extending from 9p23 to 9p21.2 was previously identified as a critical region for the 9p duplication syndrome. These results suggested that the apparently balanced de novo translocations could produce cryptic deletions or duplications, and the precise mapping of the abnormal area may improve clinical management.     

Trisomy 9p resulting from maternal 9/21 translocation

Summary The clinical picture found in a child with trisomy 9p confirmed that this chromosomal syndrome is a entity, which arises from maternal translocation t(9;21).     

Trisomy 9p in a girl whose mother has a translocation t(9;20)(q12;p13)

Summary R banding of the fine structure of the chromatids has enabled us to study a new case of trisomy for the short arm of chromosome 9. The syndrome+9p was due to nondisjunction of a maternal translocation t(9;20)(q12;p13).     

Partial trisomy 17q and monosomy 9p due to a familial translocation.

Described is an infant with partial trisomy 17q and monosomy 9p [46,XX,-9,+der(9)t(9;17)(p21;q23)] due to adjacent-1 segregation of a maternal balanced reciprocal translocation. Characteristic clinical features of both partial 17q trisomy and monosomy 9p are present, but the former syndrome is less recognisable in this infant than in previously reported cases due to the concomitant 9p monosomy.     

Familial (9;11)(p22;p15.5)pat translocation and XX sex reversal in a phenotypic boy with cryptorchidism and delayed development

We describe a patient with the co-occurrence of a familial 9;11 reciprocal translocation and an XX sex reversal. The patient had cryptorchidism, delayed development, dysmorphic features and attention deficiency hyperactive disorder (ADHD). The proband's karyotype was 46,XX,t(9;11)(p22;p15.5) and he was positive for SRY gene. The father was found to be the carrier of the similar translocation. The co-occurrence of XX sex reversal and autosomal reciprocal translocation has not been described previously. The possible reasons for the manifestation of features other than those found in XX sex reversal is described.     

Trisomy 9p with i(9p) and t(9q18p)

Summary The trisomy 9p syndrome in a 2-year-old girl with moderate mental retardation is presented. She has a unique karyotype with a de novo isochromosome 9p and a translocation between 9q and 18p.     

A familial "balanced" 3;9 translocation with cryptic 8q insertion leading to deletion and duplication of 9p23 loci in siblings.

A child with phenotypic features of the 9p- syndrome, including metopic craniosynostosis, small ears, abdominal wall defect, and mental retardation, as well as hypopigmentation, was found to have a cytogenetically balanced 3;9 translocation, with breakpoints at 3p11 and 9p23, inherited from his phenotypically normal father. Molecular analysis showed heterozygous deletion of the TYRP (tyrosinase-related protein) locus, as well as loci D9S157, D9S274, D9S268, and D9S267, in the child but in neither parent. FISH analysis of the proband''s father indicated that loci deleted in his son, including TYRP, were present on neither the der(3) nor the der(9) translocation products but had been inserted into the long arm of chromosome 8. Therefore, the apparent deletion of these loci in the proband was the result of meiotic segregation of the father''s 3;9 translocation chromosomes together with his normal chromosome 8 (not bearing the insertion from 9p23). Neither the deletion of these 9p23 loci from the translocation chromosomes nor their insertion into 8q was detectable by standard chromosome banding techniques. The proband''s sister exhibited speech delay, mild facial dysmorphism, and renal malformation, and her karyotype was 46,XX. Molecular analysis showed that she had inherited normal chromosomes 3 and 9, as well as the chromosome 8 with the insertion of 9p23 material, from her father.(ABSTRACT TRUNCATED AT 250 WORDS)     

An apparent balanced translocation [t(9;11)(p21.2;p14.2)] in a neonate with dysmorphic features.

The role of so called balanced translocations in human morphogenesis remains puzzling. An eleven month old hispanic female was referred for neurological evaluation. The major dysmorphic features include: epicanthal folds, flat nasal bridge, small mouth, micrognathia, low set ears and cleft-palate. The cytogenetic findings by multiple banding techniques revealed an apparent balanced translocation involving chromosomes 9p and 11p i.e. 46,XX,t(9;11)(p21.2;p14.2) which, according to the authors, has not been previously reported.     

Concordant congenital malformations in twins with inherited translocation: t(9p-;13q+)

Summary Several members of a family with a translocation between the short arm of chromosome 9 and the long arm of chromosome 13 (9p-;13q+) are presented. Although the translocation found in various members of the family looked alike and appeared to be balanced, the clinical features were different. The like-sex twins displayed some features of 9p monosomy syndrome, whereas their mother and maternal grandmother, who apparently had the same translocation, showed only a few features of 9p- syndrome in addition to mild mental retardation. We suggest that a minute deletion of the short arm of chromosome 9 may cause features of 9p- syndrome and that the clinical features of this syndrome in older individuals may be too mild for the clinical diagnosis to be possible.     

Boy with seizures (West syndrome) and distal 7q duplication syndrome due to an unbalanced 7q;9p translocation

We report a 15 month old boy with prominent metopic suture, epicanthal folds, strabismus, low-set ears, microretrognathia, large anterior fontanel, bilateral simian creases, muscular hypotonia, and severe psychomotor retardation. He also had West syndrome. An electroencephalogram showed hypsarrythmia, and cranial MR indicated a myelinisation delay. Standard karyotyping showed additional material on one chromosome 9p. Using FISH, a terminal 7q duplication spanning 26 Mb in size and a terminal 9p deletion sized (at least) 9.1 Mb were identified. The father had a karyotype of t(7;9)(q33;p23) and the mother's karyotype was normal. The boy presented typical facial features of the distal 7q duplication syndrome but no genital anomalies attributable to his distal 9p deletion. We assume that the severe epilepsy is likely due to the trisomy 7q.     

Molecular analysis of a reciprocal translocation t(5;11)(q11;p13) in a WAGR patient

Summary Most patients with the complex association aniridia — predisposition to Wilms' tumor (WAGR syndrome) present with a de novo constitutional deletion of band 11p13. We report a patient with WAGR syndrome and a reciprocal translocation between chromosomes 5 and 11 t(5;11)(q11;p13). High resolution banding cytogenetic analysis and molecular characterization using 11p13 DNA markers showed a tiny deletion encompassing the gene for CAT but sparing the gene for FSHB. This suggests that syndromes associated with apparently balanced translocations may be due to undetectable loss of material at the breakpoint(s) rather than to breakage in the gene itself.     

4p- syndrome in a girl with translocation t(1;4)(q11;p16)mat

Summary A newborn girl had features of the 4p- syndrome. Cytogenetic studies of the mother showed a translocation t(1;4)(q11;p16). The proband had the translocation, but the band 4p16 had been lost.     

Familial unbalanced translocation t(8;15)(p23.3;q11) with uniparental disomy in Angelman syndrome

A 29-year-old male with Angelman syndrome and an unbalanced reciprocal translocation, 45,XY,-8,-15,+der(8),t(8;15)(p23.3;q11)pat, was evaluated with DNA studies. These showed the underlying mechanism to be paternal uniparental disomy. This is the second case reported of Angelman syndrome that has resulted from a familial unbalanced reciprocal translocation.     

Paternal reciprocal translocation t(11;16)(p13;q24.3) in a Silver-Russel syndrome patient

We describe a 7-month-old male child with Silver-Russel syndrome (SRS) phenotype, presented with two major clinical features: low birth weight, short stature, and minor features, such as macrocephaly, clinodactyly, essential for the diagnosis of SRS. Routine cytogenetic studies with GTG-banding showed 46,XY,t(11;16)(p13;q24.3). Fluorescence in situ hybridisation (FISH) with single copy probes BAC (11p13) and PAC (16q24.3), showed a reciprocal translocation. Chromosomal analysis of the mother was normal and the phenotypically normal father had apparently identical translocation t(11;16)(p13;q24.3). The disruption of growth factor genes at 11p and 16q breakpoint regions due to reciprocal translocation in the father might have caused SRS phenotype in the child.     

Phenotypic and cytogenetic spectrum of 9p trisomy

Trisomy 9p is one of the most frequent autosomal anomalies compatible with long survival rate. The spectrum of clinical severity in trisomy 9 roughly correlates with the extent of trisomic chromosome material. Trisomy 9p is a clinically well delineated syndrome and of all stigmata craniofacial dysmorphism is most specific. In this study we report five cases with de novo trisomy 9p. The study aimed at the identification of the genotype/phenotype correlations in patients with different breakpoints. GTG banding, DAPI stain, whole chromosome paint, centromere, telomere and 9p21 specific locus probes demonstrated that partial trisomy 9p in case 1 was due to isochromosome 9p with translocation of the long arm of re-arranged chromosome 9 onto the short arm of chromosome 13, cases 2 and 3 had intrachromosomal duplication of the short arm of chromosome 9 [dup(9)(p21p24)], case 4 had "classical" 9p trisomy and case 5 had duplication of whole short arm and part of the long arm of chromosome 9 (partial 9 trisomy). Although cases 1 to 4 had trisomy involving 9p, cases 1 and 2 exhibited the classical clinical manifestations of 9p trisomy, while cases 3 and 4 had additional features overlapping with Coffin-Siris syndrome. The present study strengthens the association of Coffin-Siris syndrome and 9p, the significance of such observations may point to possible gene location of Coffin-Siris syndrome on 9p. Case 5 had additional manifestations more than those typical of trisomy 9p which could be due to duplication of 9q21 region. Wide gap between 1st and 2nd toes, observed in the studied cases, can be added to the phenotype of this trisomy. Three of our cases had brain malformations, case 3 had dilated ventricles with hypogenesis of corpus callosum, case 4 had agenesis of corpus callosum, and case 5 had Dandy-Walker malformation. We also suggest that dosage effects of genes located in 9pter-q22 contribute to the etiology of Dandy-Walker syndrome. We recommend MRI studies as a routine in all cases with trisomy 9p.     

9;21相互易位携带者生育多例9p部分三体患者细胞遗传学分析

在河南南阳收集到一个家系4代23人, 其中6人患先天性智力障碍, 具有轻度的面部和小母指畸形等特点, 先证者伴随有癫痫的发生。采用常规的外周血培养染色体G带分析, 发现先证者的核型为：46, XY, der(21) t(9; 21) (9p22.2; 21q22.3)pat, 是部分9p三体。对该家系其他成员的染色体进行分析, 发现所有患者均为部分9p三体, 异常染色体均来自9号与21号染色体平衡易位携带者染色体相互易位的异常分离, 因此这是一个部分9p三体综合征家系。而重复区段发生在9号染色体短臂远端一半区域(9pter→9p21)内, 该区是关键区, 导致智力障碍和面容轻微畸形。     

Partial trisomy 6p due to familial translocation t(6;20)(p21;p13)

Summary Cytogenetic findings in a case of partial trisomy 6p due to a translocation t(6;20)(p21;p13) and eleven balanced translocation heterozygotes are described.The clinical data of the proposita are compared with those of five other published cases. A partial trisomy 6p syndrome is postulated, characterized by: low birth weight, psychomotor retardation, craniofacial abnormalities (such as high prominent forehead, large fontanel, wide sagittal suture, blepharoptosis, low-set and/or malformed ears), congenital heart malformation, small kidneys, and proteinuria. Linkage studies have shown that the breakpoint in chromosome 6 involved in this translocation is close to the HLA gene cluster.     

Partial trisomy 4q and monosomy 9p resulting from a familial translocation t(4;9)(q27;p24) in a child with choanal atresia.

A male infant with a deletion of 9p and concomitant duplication of 4q: 46,XY, der(9)t(4;9)(q27;p24), is described. Parental chromosome analysis showed a balanced maternal translocation. To our knowledge, the above cytogenetic and clinical abnormalities have not been described previously. A phenotype comparison is presented with previously reported cases concerning a deletion of 9p and a duplication of 4q.     

Familial C/D translocation t(9;13)(9p23;13q21) in a male associated with recurrent abortion

Summary A familial reciprocal translocation, established by R-banding as t(9;13) (9p23; 13q21), is described in a phenotypically normal male carrier, whose father is also a balanced carrier and wife had four consecutive spontaneous abortions. The role of translocation in reproductive failure through production of chromosomally unbalanced gametes or by impairment of the spermatogenesis is briefly discussed.     

Trisomy 9p due to paternal translocation, t(9;13) (q13;q12).

A 16-year-old girl with trisomy 9p is described. She had a short stature, severe mental retardation and the following abnormal clinical findings: peculiar face with hypertelorism, downward slanting palpebral fissures, convergent strabismus, a bulbous nose with broad and prominent bridge, short upper lip, narrow, high-arched palate; short neck with low hairline; severe kyphoscoliosis and a congenital clubfoot deformity; hypoplasia and dysplasia of several phalanges of the fingers and toes and some nails, a delay by about 6 years in bone age, and remarkable dermatoglyphic patterns. The father and 3 other family members carried a balanced translocation between chromosomes 9 and 13, t(9;13)(q13;q12).