Partial Trisomy 1q Research Articles

NFκB2 gene duplication is associated with fetal pyelectasis in partial trisomy 10q (10q24.1 → qter)

<i>NF</i>κ<i>B2</i> gene duplication is associated with fetal pyelectasis in partial trisomy 10q (10q24.1 → qter)

Prenatal diagnosis of mosaic trisomy 8q studied by ultrasound, cytogenetics, and array‐CGH

Mosaic trisomy 8, also known as Warkany syndrome, has a well-characterized constellation of phenotypic findings. Partial trisomy 8, including mosaic cases, has also been reported, with outcome and counseling dependent on the chromosomal segment involved and whether accompanied by partial aneuploidy for other chromosomes. We present a case of a fetus mosaic for trisomy of the entire long arm (q) of chromosome 8 without additional chromosomal aberrations. The diagnosis was made by amniocentesis performed following an 18 week sonogram that showed multiple fetal anomalies. Mosaicism for trisomy 8q was confirmed by routine karyotyping and fluorescent in situ hybridization (FISH) analysis. The case proved useful for testing the sensitivity of array comparative genomic hybridization (array-CGH) with respect to segmental trisomy in the presence of chromosomal mosaicism. The phenotype of this fetus, which appears to be the first reported case involving mosaic trisomy 8 for the entire q arm of the chromosome, is described and compared to previously reported cases involving partial trisomy 8q.

Blepharophimosis and mental retardation (BMR) phenotypes caused by chromosomal rearrangements: Description in a boy with partial trisomy 10q and monosomy 4q and review of the literature

Blepharophimosis is a rare congenital anomaly of the palpebral fissure which is often associated with mental retardation and additional malformations. We report on a boy with blepharophimosis, ptosis and severe mental retardation carrying an unbalanced 4;10 translocation with terminal duplication of 10q [dup(10)(q25.1→qter)] and monosomy of a small terminal segment of chromosome 4q [del(4)(34.3→qter)]. Detailed clinical examination and review of the literature showed that the phenotype of the patient was mainly determined by the dup(10q). This paper reviews the chromosomal aberrations associated with BMR (blepharophimosis mental retardation) phenotypes. Searching different databases and reviewing the literature revealed 14 microscopically visible aberrations (among them UPD(14)pat) and two submicroscopic rearrangements causing blepharophimosis and mental retardation (BMR) syndrome. Some of these rearrangements—like the terminal dup(10q) identified in our patient or interstitial del(2q)—are associated with clearly defined phenotypes and can be well distinguished from each other on basis of clinical examination. This paper should assist clinicians and cytogeneticists when evaluating patients with BMR syndrome.

Partial trisomy 13q22-qter associated to leukoencephalopathy and late onset generalised epilepsy

The partial trisomy 13q.22 is an uncommon chromosomopathy. We present a case with a partial trisomic component 13q22 and a monosomic component 5p15 from paternal origin. This patient developed early menopause and major neurological disorders as leukoencephalopathy, late onset generalised epilepsy and stroke. She also had fatty acids disturbances and their potential relation to the neurological disorders and early menopause is discussed. The presented case illustrates the phenotype of 13q22-qter in adult age and reaffirms the importance of studying the karyotype of any patient with seizures or leukoencephalopathy particularly when there are associated other clinical features including stroke at a young age, fatty acids disturbances, microcephaly, hypotelorism, short neck, hemangiomata, short fingers or distal swell in thumbs.

Partial Trisomy 1q41 Syndrome Delineated by Whole Genomic Array Comparative Genome Hybridization

Partial trisomy 1q syndrome is a rare chromosomal abnormality. We report on a male infant with 46,XY,der(11)t(1;11)(q41;p15.5) due to unbalanced segregation of the maternal reciprocal balanced translocation 46,XX,t(1;11)(q41;p15.5). The baby presented with a mild phenotype, characterized by a triangular face, almond-shaped eyes, low ears, short stature with relatively long legs, and mild psychomotor retardation. We utilized whole genomic array comparative genome hybridization (CGH) with 4,000 selected bacterial artificial chromosomes (BACs) to define the chromosomal breakpoints and to delineate the extent of the partial trisomy in more detail. To our knowledge, this is the first case of nearly pure "partial trisomy 1q41" defined by whole genomic array CGH.

Partial proximal 10q trisomy: a new case associated with biliary atresia

Herein we describe a unique case of partial proximal 10q trisomy presenting biliary atresia, anal anteposition and cardiac malformation. The 10q duplication was confirmed by G banding on prophase chromosomes. A review of the literature confirmed that the patient displayed characteristic dysmorphic features of the recently defined partial proximal trisomy 10q syndrome and emphasized the interindividual variability of visceral malformations.

P50.11: Prenatal diagnosis of partial trisomy 3q with omphalocele in the first trimester of pregnancy

P50.11: Prenatal diagnosis of partial trisomy 3q with omphalocele in the first trimester of pregnancy

Distal partial trisomy 1q: report of two cases and a review of the literature

We report on two cases with partial trisomy 1q syndrome. One case was a mid-trimester fetus with multiple malformations that was prenatally diagnosed with a de novo distal partial trisomy 1q. Prenatal ultrasound at 24th gestational week demonstrated the presence of cleft lip and palate, increased biparietal diameter and decreased abdominal circumference. Cytogenetic analysis (GTG banding) and subsequent fluorescence in situ hybridization (FISH) using whole chromosome paint 1 and multicolor banding (MCB) demonstrated an aberrant karyotype 46,XY,dup(1)(q31q43 approximately 44). The second case was a newborn male infant with multiple congenital malformations. He had a derivative chromosome 18 as a result of a maternal insertion involving chromosomes 1 and 18. Further analyses including MCB showed his karyotype as 46,XY,ins(18;1)(q22;q23q31.1 approximately 32). The present cases and a review of the literature suggest that partial trisomy of the long arm of chromosome 1 is a distinct clinical entity.

Prenatal diagnosis of partial trisomy 1q and monosomy X in a fetus with a congenital lung lesion and hydrops fetalis

We report on the prenatal diagnosis of partial trisomy 1q and monosomy X in a fetus with a congenital lung lesion and hydrops. The finding of hydrops in a fetus with a small lung lesion, congenital cystic adenomatoid malformation (CCAM) volume to head circumference ratio (CVR) 0.78, prompted cytogenetic analysis of amniotic fluid, revealing an unbalanced translocation between chromosomes X and 1 [46,X,der(X)t(X;1)(p11.2;q25 or q31)]. The incidence of chromosomal abnormalities with CCAM lesions is estimated at 1.6%. This is the first reported case of prenatally diagnosed partial trisomy 1q and monosomy X presenting as a fetal lung lesion and hydrops.

Sacrococcygeal teratoma in a fetus with prenatally diagnosed partial trisomy 10q (10q24.3→qter) and partial monosomy 17p (p13.3→pter)

Clinical features of the distal 10q trisomy syndrome consist of mental retardation, facial dysmorphism and renal and cardiac anomalies. The presence of a sacrococcygeal teratoma (SCT) in a fetus with distal 10q trisomy has not been reported yet. A 33-year-old, G5, P2 woman with a singleton pregnancy was referred to our clinic at 24 weeks of gestation for further evaluation of a fetal sacral exophytic mass. Detailed fetal sonographic examination together with chromosomal analysis by amniocentesis was performed. The scan revealed a large SCT together with a persistent right umbilical vein, cardiomegaly, bilateral mild hydronephrosis and intrauterine growth retardation. The fetal karyotype showed distal 10q trisomy (10q24.3-->qter) distal monosomy 17 (p13-->pter). The fetus died after a preterm delivery at 28 weeks of gestation. Postnatal examination confirmed the prenatal findings and added the typical facial features of this syndrome, which consisted of prominent forehead, small nose with depressed nasal bridge, micrognathia and bow-shaped mouth. This case provides further evidence of a possible association between chromosomal aberrations in SCTs.

A fourteen years follow-up of a case of partial trisomy 12q and monosomy 12p recombinants of a familial pericentric inversion of chromosome 12: Clinical, cytogenetic and molecular observations

Partial trisomy 12q and monosomy 12p lead to multiple malformation syndromes. Only four cases were previously reported with the association of these two aneusomies resulting from a familial pericentric inversion of chromosome 12. We report on the clinical, cytogenetic and molecular findings in a boy with an unbalanced karyotype which resulted from a familial pericentric inversion of chromosome 12. The patient was evaluated at birth and followed up until 14 years of age. He showed severe mental retardation, seizures, and dysmorphic features related both to a trisomy 12q and a monosomy 12p. Chromosome breakpoint BAC-FISH mapping revealed that the rec(12) chromosome had a terminal deletion of a 6.7 Mb region extending from 12pter to 12p13.31 and a duplicated region of 19.8 Mb extending from 12qter to 12q24.13. The findings from the case reported here emphasize the occurrence of some consistent clinical features and illustrate the deficiencies associated with the recombinants from the inversion inv(12)(p13.31q24.13)mat.

Germ Cell Tumor Showing Partial Trisomy 1 in a Gonadectomized Intersex Child With Monosomy X and Double Y Mosaicism

High incidence of germ cell tumors arising from dysgenetic gonads in patients with sexual chromosome abnormalities has been described, especially in patients with a Y chromosome bearing cell line. Here we report a 14-year-old patient with ambiguous genitalia. Constitutional karyotype showed 45,X/46,X,derY [?t(Yp;Yq)] mosaicism. The patient developed an abdominally located mixed malignant germ cell tumor 5 years after the removal of the dysgenetic gonads. Tumor karyotype showed partial trisomy 1q, a derivative 8q, and a hyperdiploidy with +X, +7, +12, +15, +19, +21, and an unidentified marker.

Primary ovarian failure in a mentally retarded woman with a de novo unbalanced X;autosome translocation

To describe the clinical findings of a patient with a de novo unbalanced X;autosome translocation. Descriptive case study. Mackay Memorial Hospital, National Yang-Ming University, China Medical University, China Medical University Hospital, and Chung Shan Medical University. A 33-year-old woman with primary ovarian failure, moderate mental retardation, and mild phenotype of facial dysmorphism. None. Ultrasound, cytogenetic analysis, and laboratory studies of hormones. Laboratory studies revealed the following values: FSH level 72.48 mIU/mL (normal women: <40 mIU/mL), LH level 32.87 mIU/mL (normal women: <21 mIU/mL), and E(2) level <20 pg/mL (normal women up to 375 pg/mL), confirming primary ovarian failure. The PRL level was normal. Spectral karyotyping and G-banding cytogenetic analysis revealed a derivative X chromosome containing additional chromosomal material derived from the distal long arm of chromosome 5. The derived chromosome X had break points at Xq27.3 and 5q32, resulting in monosomy Xq (Xq27.3-->qter) and partial trisomy 5q (5q32-->qter). The patient's karyotype was 46,X,der(X)t(X;5)(q27.3;q32). The parental karyotypes were normal. This is the first report of partial monosomy Xq (Xq27.3-->qter) and partial trisomy 5q (5q32-->qter). The present case provides evidence for the occurrence of primary ovarian failure and mental retardation in females with unbalanced X;autosome translocations.

Prenatal diagnosis of a partial 6q trisomy: a case report

To present a case of partial 6q trisomy diagnosed prenatally. A 28-year-old woman underwent genetic amniocentesis at 23 weeks of gestation on the detection of an enlarged nuchal fold (8.5 mm), which was the only clinical abnormality on routine ultrasound examination. Fetal karyotyping revealed a partial trisomy 6q (q21-q22) caused by a balanced maternal chromosomal insertion. A female infant was delivered at 38 weeks of gestation. At birth, minor dysmorphisms were recorded, which included low set ears, macrocephaly and a webbed neck. At 17 months of age, neurological developmental assessment was normal. The appearance of phenotypic expression and clinical outcome of partial 6q trisomy depends on the specific chromosomal region involved in the segmental aneusomy.

Coexistence of neocentromeric marker 3q and trisomy 3 in two different tissues in a 3-year-old boy with peripheral T-cell lymphoma: support for a gene dosage effect hypothesis

A very small supernumerary de novo marker chromosome was ascertained during cytogenetic diagnosis of a 3½-year-old boy with peripheral T-cell lymphoma, unspecified. The marker, which was C-band and α-satellite DNA negative, was identified in the pleural effusion and involved cervical lymph node whereas the involved bone marrow cells had trisomy 3 as a clone. The neocentromere marker was characterized by multiple probes demonstrating an inversion duplication of the distal portion of chromosome 3q involving the BCL6 gene. Whole or partial trisomy 3q represents one of the most recurrent chromosomal abnormalities occurring in T-cell lymphomas, suggesting that the 3q contains a critical region for the pathogenesis of T-cell lymphoma. Our present case showed that the critical region may reside within the neocentromere marker 3q27∼q29 in this case in particular and revealed a different mechanism in increasing gene dosage rather than gene disruption. In addition, this type of neocentromere is one most often reported in constitutional cases. Here, we report its presence in cancer for the first time.

Fluorescence in situ hybridization using the subtelomeric 11q probe as a diagnostic tool for congenital thrombocytopenia

Dear Editor, Thrombocytopenia in the neonate is often a life-threatening disorder. Adequate clinical management requires a prompt and accurate diagnosis of the underlying pathology. While acquired thrombocytopenia secondary to the use of certain drugs, such as quinine, heparin, nonsteroidal antiinflammatory agents, histamine blockers, and most chemotherapeutic agents, allopurinol and alcohol, idiopathic thrombocytopenic purpura (ITP) or other failures of thrombopoiesis, such as liver cirrhosis or lack of vitamin B12, are common, congenital disorders of platelet production have recently gained increasing attention. With the discovery of the underlying genetic changes, disorders like X-linked macrothrombocytopenia (mutation in GATA-1) or congenital amegakaryocytic thrombocytopenia (mutations in C-MPL) can now be defined on a molecular basis [1]. Children with these disorders usually do not have additional symptoms other than thrombocytopenia. Patients with Jacobsen syndrome, a rare chromosomal disorder with terminal 11q deletion, can present with growth and mental retardation, trigonocephaly, facial dysmorphism (hypertelorism, epicanthus, ptosis, broad nasal bridge, short nose with anteverted nostrils, high arched palate, retrognathia, carp-shaped upper lip, and low-set dysmorphic ears), abnormal brain structures, congenital heart defects, and genitourinary anomalies in addition to thrombocytopenia [2, 3]. Because of its variable expression, Jacobsen syndrome may not be clinically recognized. Symptoms and severity depend on the size of the deleted region [2]. The genes involved were not identified so far. Differential diagnosis of Jacobsen syndrome includes other chromosomal disorders like 3p− syndrome, 9p− syndrome, and partial distal trisomy 3q. Because Jacobsen syndrome is a contiguous gene syndrome, the size of the deleted region of 11q correlates with a defined phenotype [4]. Only thrombocytopenia seems to be present in nearly every case independent of the breakpoint [5, 6]. In this study, we report on a full-term female neonate with petechiae, intracranial bleeding, cardiac defects, and facial dysmorphia. The platelet count was 26,000/μl, and platelets were normal in size. Mild anemia (hemoglobin 9.5 mg/dl) was attributed to previous bleeding, while the white blood and differential count were normal. In the bone marrow, a high number of micromegakaryocytes were noted. To prevent further bleeding, platelet transfusions were administered regularly. At the age of 2 months, the platelet count spontaneously rose to 70,000/μl to normalize within the subsequent months. Fluorescence R-banding, fluorescence in situ hybridization (FISH), and array-comparative genomic hybridization (CGH) from bone marrow samples and peripheral blood were carried out as previously described by Gadzicki et al. [6]. For the FISH analysis, commercially available locusspecific probes for the subtelomeric region of 11q and for the ataxia-telangiectasia locus (ATM) in 11q22–q23 were used (Vysis, Downers Grove, IL, USA). For both probes used, the cut-off level was defined as 10%. Chromosome banding analysis on bone marrow cells of the newborn showed a structural chromosome aberration, most probably a terminal deletion with a breakpoint in Ann Hematol (2006) 85:883–885 DOI 10.1007/s00277-006-0177-2

Prenatal diagnosis of congenital chylothorax associated with de novopartial trisomy 12q (12q21.2→qter)

Prenatal diagnosis of congenital chylothorax associated with <i>de novo</i>partial trisomy 12q (12q21.2→qter)

Molecular cytogenetic analysis of de novo dup(5)(q35.2q35.3) and review of the literature of pure partial trisomy 5q

An 11-year-old girl presented with the phenotype of microcephaly, moderate mental retardation, motor retardation, short stature, strabismus, brachydactyly, and facial dysmorphism. She had undergone surgery for inguinal hernias. Detailed examinations of the heart and other internal organs revealed normal findings. Her karyotype was 46,XX,dup(5)(q35.2q35.3) de novo. Molecular cytogenetic analysis showed a paternally derived 5q35.2 --> q35.3 direct duplication and led to a correlation between the particular genotype and phenotype. This is the first description of a direct duplication of 5q35.2 --> q35.3. Our case represents the smallest distal duplication of chromosome 5q that is not associated with congenital heart defects. Our case also represents the smallest distal duplication of chromosome 5q that is associated with short stature and microcephaly. Mutations or deletions of the NSD1 gene, mapped to 5q35.2 --> q35.3, has been known to cause Sotos syndrome with cerebral gigantism, macrocephaly, advanced bone age and overgrowth. Our case provides evidence that the gene dosage effect of the NSD1 gene causes a reversed phenotype of microcephaly and short stature.

Prenatal findings and molecular cytogenetic analyses of partial trisomy 12q (12q24.32→qter) and partial monosomy 21q (21q22.2→qter)

To present the prenatal findings and molecular cytogenetic analyses of partial trisomy 12q and partial monosomy 21q, and a review of the literature. Amniocentesis was performed at 23 gestational weeks in a 33-year-old woman because of abnormal sonographic findings. Amniocentesis revealed a derivative chromosome 21, or der(21), with a deletion on the region of 21q22.2 and an addendum of a small chromosomal segment of unknown origin. The maternal karyotype was subsequently found to be 46,XX,t(12;21)(q24.32;q22.2). Level II ultrasound showed microcephaly, micrognathia, a ventricular septal defect, and rocker-bottom feet. The pregnancy was terminated. A malformed infant was delivered without the phenotype of holoprosencephaly (HPE). Fluorescence in situ hybridization (FISH) and polymorphic DNA markers were used to investigate the involved chromosomal segments. FISH study showed the absence of the signal of 21q subtelomeric probe and the presence of the signal of 12q subtelomeric probe in the der(21). The fetal karyotype was 46,XY,der(21) t(12;21)(q24.32;q22.2)mat. Genetic marker analysis showed a deletion at 21q22.2 and a breakpoint between D21S156 (present) and D21S1245 (absent). The deleted segment was measured about 4.5 Mb encompassing the HPE critical region. Molecular genetic analyses help in determining the prenatally detected unbalanced cryptic translocation as well as parental balanced subtle translocation. A duplication of 12q24.32-->qter and a deletion of 21q22.2-->qter may be associated with prenatal sonographic findings of microcephaly, borderline ventriculomegaly and cerebellar hypoplasia, micrognathia, a ventricular septal defect, and rocker-bottom feet. Haploinsufficiency of the HPE critical region at 21q22.3 may not cause an HPE phenotype.

Prenatal diagnosis and molecular cytogenetic characterisation of a small de novo interstitial duplication 16q11.2‐q13

We describe the first prenatally detected case of a small de novo interstitial duplication of chromosome 16q. This chromosomal aberration is extremely rare. Amniocentesis was indicated by advanced maternal age only. Ultrasound examinations of the foetus showed no abnormalities. Conventional and molecular cytogenetic analyses on cultured amniocytes by comparative genomic hybridisation (CGH) and fluorescence in situ hybridisation (FISH) using partial chromosome paints and a locus-specific YAC clone revealed a de novo direct duplication of the chromosomal region 16q11.2-q13 leading to a partial trisomy 16q (46,XX,dup(16)(q11.2q13)). There are only five postnatal reports of comparable duplications involving this chromosomal region. These patients presented with little or no associated dysmorphic features but with significant neurodevelopmental delay and severe behavioural problems. After genetic counselling, the parents opted for termination of pregnancy. Post-mortem examination showed slight facial dysmorphic signs, minor dysgenesis of the ovaries and an atypical outflow of the arteria thyroidea ima.