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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Research on the subtelomeric region has considerably increased because this chromosome segment (1) keeps the chromosome number constant, (2) intervenes in cancer and cell senescence processes, (3) presents more crossovers than other regions of the genome and, (4) is the site of cryptic chromosome aberrations associated with mental retardation and congenital malformations. Quantitative microphotometrical scanning and computer graphic image analysis enables the detection of differentially distributed Giemsa-stained structures in T-banded subtelomeric segments of human and Chinese hamster ovary (CHO) chromosomes. The presence of high density stain patterns in the subtelomeric region was confirmed using endoreduplicated chromosomes as a model. Besides, prolonging the incubation in the T-buffer, specific holes were induced in subtelomeric segments. Hole specificity was confirmed inducing them in complex CHO chromosome aberrations obtained by AluI. The method was also used to detect minute sister chromatid exchanges in the T-banded subtelomeric area (t-SCEs). The presence of t-SCEs was suspected to reflect, at the microscope level, the high crossover activity prevailing in the region. Due to the fact that the fluorescent signals obtained with subtelomeric probes seem to be colocalized with subtelomeric high density areas, measurements on the position of both structures with respect to the diffraction and chromosome edges were carried out. Data obtained showed comparable values suggesting that the high density segments were located where telomeric probes usually fluoresce. The possible relationship of the high density patterns, the production of specific holes, the localization of fluorescent areas and the detection of minute SCEs in the subtelomeric segment observed in T-banded CHO and human chromosomes is briefly reviewed.
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PMID:Cytological indications of the complex subtelomeric structure. 1516 27

We report clinical, cytogenetic, and molecular cytogenetic studies on four patients with subtle or submicroscopic 7q36 deletions either of de novo origin or resulting from a cryptic parental translocation. Fluorescence in situ hybridization (FISH) studies indicated that in all four patients, the Sonic Hedgehog gene (SHH) and the homeobox gene HLXB9, among others, are comprised in the deletions. Besides mental retardation and short stature, all patients showed only minimal manifestations of the holoprosencephaly (HPE) spectrum and only one displayed symptoms of the Currarino syndrome. Patient 1 had a de novo 7q36.1-qter deletion and showed microcephaly, ptosis, sacral agenesis, tethered cord, but no structural brain anomaly. Patient 2 had a submicroscopic de novo 7q36 deletion detected by FISH, and showed facial and cerebral microsigns of the HPE spectrum. Patient 3 had a 7q36 deletion found by subtelomere FISH testing that was the unbalanced product of a subtle maternal 7q;10q translocation. She presented facial and ocular microsigns, but no structural abnormality of the brain. Patient 4 showed no specific syndromal pattern and was found to have a cryptic unbalanced de novo translocation of the terminal parts of chromosomes 7q and 9p by subtelomere FISH. Patients 2, 3, and 4 represent the first report of a de novo submicroscopic 7q36 deletion, the second report of a familial subtle translocation of 7q36, and the first report of an unbalanced de novo submicroscopic translocation of 7q36, respectively. Our results stress the importance of 7q36 deletion studies by FISH in patients with microsigns of the HPE spectrum.
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PMID:Minimal clinical expression of the holoprosencephaly spectrum and of Currarino syndrome due to different cytogenetic rearrangements deleting the Sonic Hedgehog gene and the HLXB9 gene at 7q36.3. 1521 64

The clinical phenotype of patients with ring chromosome 22 includes mental retardation with severe language impairment, hypotonia, and dysmorphic facial features. In recent years an increasing number of patients with microscopic as well as cryptic terminal deletion involving band 22q13 have been described and their phenotype shows clinical features overlapping with patients with ring chromosome 22. Loss of DNA in the 22q13.3 region may lead to a clinically recognizable syndrome named "22q13.3 deletion syndrome." We report a patient with a ring chromosome 22 who has hypotonia, profound mental retardation, language impairment, dysmorphic features, and behavioral disorders. To check if the critical region responsible for "22q13.3 deletion syndrome" was absent in this ring, a fluorescent in situ hybridization (FISH) analysis using a probe corresponding to the ARSA locus was performed. In our patient, only one ARSA signal could be detected, indicating that the deletion encompassed the critical 22q13.3 region. A more detailed analysis of the deletion extent then was performed using a panel of fluorescent probes located within 22q13. These experiments allowed the identification of the breakpoint between CTA-299D3 and RP5-925J7 probe, located in 22q13.32. Deletion extent could be estimated to be about 2.5 Mb, and this larger deletion may explain the severity of clinical features observed in our patient.
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PMID:Characterization of the phenotype and definition of the deletion in a new patient with ring chromosome 22. 1537 17

Thirty patients have been described with cytogenetically visible deletion of the short arm of chromosome 6. However, subtelomeric 6p deletion detected by subtelomeric specific probes has been reported only twice. We report two new patients with terminal 6p deletion detected by subtelomeric screening using fluorescence in situ hybridization (FISH). The two patients exhibited mental retardation, ocular abnormalities, hearing loss, and a characteristic facial appearance. Detailed FISH analyses with probes covering the distal 6p25 region estimated the size of the terminal deletions to approximately 5.5 Mb and approximately 4.8 Mb. Array-based comparative genomic hybridization (array CGH) was used to confirm the cryptic deletions. Most patients with subtelomeric defects lack a characteristic phenotype. However, some of the subtelomeric deletions result in a specific phenotype, which can direct the clinician towards the diagnosis. Submicroscopic 6p deletion appears to be a recognizable clinical phenotype, and this region should be thoroughly investigated with FISH probes, including at least a subtelomeric 6p probe and a probe covering FOXC1, for patients presenting with a characteristic facial appearance, ocular abnormalities, predominantly anterior-chamber eye defects, hearing loss, and mental retardation.
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PMID:Subtelomeric 6p deletion: clinical, FISH, and array CGH characterization of two cases. 1557 19

Molecular cytogenetics allows the identification of cryptic chromosome rearrangements, which is clinically useful in mentally retarded and/or dysmorphic individuals with normal results from conventional cytogenetics analysis. We report on a 3-year-old girl with mental retardation, growth deficiency, speech delay, and dysmorphic features including hypertelorism, upslanting palpebral fissures, midfacial hypoplasia, and posteriorly rotated ears. The G-banding analysis showed a 46,XX,t(3;8)(q26.2;p21.1)mat karyotype. However, her clinical features were suggestive of the 18q syndrome. Subtelomeric FISH analysis revealed a der(18) translocated material from chromosome 17. Array-based comparative genomic hybridization (array-CGH) with subtelomeric BAC and PAC clones confirmed the abnormality and refined the breakpoints to 18q22.3-qter and 17p13.2-pter (deletion of 8.5 Mb and duplication of 3.9 Mb, respectively). This case demonstrates the diagnostic utility of combining conventional cytogenetics with molecular chromosome analyses for the identification of subtle chromosome abnormalities.
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PMID:Cryptic unbalanced translocation t(17;18)(p13.2;q22.3) identified by subtelomeric FISH and defined by array-based comparative genomic hybridization in a patient with mental retardation and dysmorphic features. 1601 83

We report on an infant who had been prenatally diagnosed with Klinefelter syndrome associated with a "de novo" pericentric inversion of the Y chromosome. A re-evaluation at 3 years of age suggested that he was also affected by Beckwith-Wiedemann syndrome (BWS). Karyotype was repeated and fluorescence in situ hybridisation (FISH) analysis revealed trisomy for 11p15.5-->11pter and a distal monosomy 18q (18q23-->qter). Parental cytogenetic studies showed that the father carried a balanced cryptic translocation between chromosomes 11p and 18q. Furthermore, the child had an extra X chromosome and a "de novo" structural abnormality of chromosome Y. Thus, his karyotype was 47,XX, inv (Y) (p11.2 q11.23), der(18) t (11;18) (p15.5;q23) pat. ish der(18) (D11S2071+, D18S1390-). Two markers on the X chromosome showed that the extra X of the child was paternally inherited. No deletions were observed on the structurally abnormal Y chromosome from any of the microsatellites studied. Clinical findings of patients with BWS due to partial trisomy 11p reveal that there is a distinct pattern of dysmorphic features associated with an increased incidence of mental retardation when comparing patients with normal chromosomes. This fact reinforces that FISH study have to be performed in all BWS patients, specially in those with mental retardation since small rearrangements cannot be detected by conventional cytogenetic techniques.
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PMID:Beckwith-Wiedemann syndrome due to 11p15.5 paternal duplication associated with Klinefelter syndrome and a "de novo" pericentric inversion of chromosome Y. 1605 7

Subtelomeric chromosomal rearrangements detected in patients with idiopathic mental retardation and dysmorphic features: Cryptic aberrations involving the subtelomeric regions of chromosomes are thought to be responsible for idiopathic mental retardation (MR) and multiple congenital anomalies, although the exact incidence of these aberrations is still unclear. With the advent of chromosome-specific telomeric Fluorescence In Situ Hybridization (FISH) probes, it is now possible to identify submicroscopic rearrangements of distal ends of the chromosomes that can not be detected by conventional cytogenetic methods. In this study, cryptic subtelomeric chromosomal aberrations were detected in two of ten patients with idiopathic MR and dysmorphic features by using FISH probes of subtelomeric regions of all chromosome arms. A cryptic unbalanced de novo translocation was detected between the subtelomeric regions of the chromosome 10p and 18p in a patient with severe mental retardation, sensorineuronal deafness and several dysmorphic features. In the other patient, with mild mental retardation and dysmorphic features, a de novo subtelomeric deletion of chromosome 2q was found. In conclusion, in both familial and sporadic cases with idiopathic MR and dysmorphic features, the detection of chromosomal aberrations including subtelomeric rearrangements is of great importance in offering genetic counseling and prenatal diagnosis.
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PMID:Subtelomeric chromosomal rearrangements detected in patients with idiopathic mental retardation and dysmorphic features. 1608 Feb 92

Screening of a large series of patients with unexplained mental retardation with a 1 Mb BAC array resulted in the detection of several cryptic chromosomal imbalances. In this paper we present the findings of array CGH screening in a 14-year-old boy with the brachytelephalangic type of chondrodysplasia punctata, mental retardation and obesity. On several occasions, cytogenetic analysis of this boy revealed a normal karyotype. Subsequent screening with array CGH resulted in the detection of a distal 9p trisomy and distal Xp nullisomy caused by an unbalanced X;9 translocation: 46,Y,der(X)t(X;9)(p22.32;p23). The identification of this de novo chromosomal rearrangement not only made accurate genetic counselling possible but also explained most of the phenotypic abnormalities observed in this patient. This study confirms the power of array CGH in the detection of subtle or submicroscopic chromosomal changes.
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PMID:Identification of an unbalanced X-autosome translocation by array CGH in a boy with a syndromic form of chondrodysplasia punctata brachytelephalangic type. 1617 25

Frequency of truly cryptic subtelomere abnormalities - a study of 534 patients and literature review. Unbalanced subtelomere chromosome rearrangements are a significant cause of mental retardation with approximately 5% of over 3000 affected individuals tested worldwide having a chromosome rearrangement of this type. Many of these abnormalities are detectable using routine karyotyping at the 550 band level and therefore are not considered to be cryptic. The frequency of truly cryptic subtelomere abnormality should be less than 5% but has not been established. In this study, we defined 'cryptic abnormality' as one not detectable at the 550 band level on routine karyotyping. Using this as one of the selection criteria, we have studied 534 individuals with mental retardation/ developmental delay (MR/DD) and referred for subtelomere study by clinical geneticists. We have identified seven cases with cryptic subtelomere abnormalities. The clinical features of the seven abnormal cases are summarized. Literature review identified five publications on the identification of subtelomere abnormalities which used similar recruitment criteria: (a) normal karyotype at the 550 band level and (b) subjects were selected for subtelomere studies. Combining the data from these studies with those of the current study, 1154 patients were tested and 30 subtelomere abnormalities were identified. We estimate the frequency of truly cryptic subtelomere abnormality to be approximately 2.6% (30/1154) in children with MR/DD who are referred for subtelomere study.
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PMID:Frequency of truly cryptic subtelomere abnormalities--a study of 534 patients and literature review. 1620 11

In recent years, subtelomeric rearrangements have been identified as a major cause of multiple congenital anomalies/mental retardation syndromes. Currently, more than 2,500 individuals with mental retardation have been tested and reported in whom subtelomeric rearrangements were detected ranging from 2% to 29%. Therefore, subtelomeric FISH analysis is indicated as a second tier test after high-resolution G-banding analysis in patients with otherwise unexplained developmental delay/mental retardation and/or multiple congenital anomalies. We describe a patient and her three maternal female cousins, all showing an undiagnosed MCA/MR syndrome, associated with the same complex subtelomeric rearrangement. Subtelomeric FISH testing performed between 3(1/2) and 18 years after the initial karyotype showed, in all four patients, distal trisomy 3q and distal monosomy 10q as follows: 46,XX,ish der(10)t(3;10)(q29;q26.3)mat(D10S2488+,D10S2490-, D3S1272+,D10Z1+). Parental subtelomeric FISH analysis showed that the proposita's mother and three of four brothers and one of two sisters had a cryptic balanced 3:10 telomere translocation. The three brothers with the balanced translocation were father to one each of the three proband's cousins. All four affected girls showed a similar phenotype with pre/postnatal growth retardation, microcephaly, severe developmental delay/mental retardation, poor/absent speech, and a distinct pattern of malformation. On examination there were coarsening of facial features with low fronto-temporal hairline; thick eyebrows; bilateral epicanthal folds; hypertelorism; prominent nose with squared nasal root and narrow alar base; low-set posteriorly rotated large ears with a prominent anthelix; high arched palate; prominent chin; hands/feet brachydactyly; bilateral squint; hypotonia; and muscle hypotrophy. A slow overall improvement was seen in all patients over time. To our knowledge, this complex subtelomeric rearrangement in our patients has never been reported so far. Monosomy 10q has recently been described either isolated or as part of a complex rearrangement involving telomeres other than the 3q. Trisomy 3q29 has not yet been reported, but our patients resembled cases with 3q26 trisomy suggesting that the critical region of duplication for this phenotype is in 3q29.
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PMID:Familial complex 3q;10q rearrangement unraveled by subtelomeric FISH analysis. 1635 44


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