1/17. A family with a grand-maternally derived interstitial duplication of proximal 15q.About 1% of individuals with autism or types of pervasive developmental disorder have a duplication of the 15q11-q13 region. These abnormalities can be detected by routine G-banded chromosome study, showing an extra marker chromosome, or demonstrated by fluorescence in situ hybridization (FISH) analysis, revealing an interstitial duplication. We report here the molecular, cytogenetic, clinical and neuropsychiatric evaluations of a family in whom 3 of 4 siblings inherited an interstitial duplication of 15q11-q13. This duplication was inherited from their mother who also had a maternally derived duplication. Affected family members had apraxia of speech, phonological awareness deficits, developmental language disorder, dyslexia, as well as limb apraxia but did not have any dysmorphic clinical features. The observations in this family suggest that the phenotypic manifestations of proximal 15q duplications may also involve language-based learning disabilities.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
2/17. Case report: angelman syndrome in an individual with a small SMC(15) and paternal uniparental disomy: a case report with reference to the assessment of cognitive functioning and autistic symptomatology.The case of a 15-year-old male with angelman syndrome, paternal uniparental disomy of chromosome 15, and a small supernumerary marker chromosome is discussed. Assessment of cognitive functioning revealed an uneven profile of ability across different domains; in particular, receptive language ability was found to be superior to expressive language ability, whilst both gross and fine motor skills were found to be relatively well developed. Assessment using the Autism Diagnostic observation Schedule showed very little evidence of autistic symptomatology. The patient showed an interest in social interaction and used a variety of methods to communicate, including some gestures and several single words. A clinical history revealed febrile convulsions during childhood but an absence of seizures in the previous 5 years. The patient was not hypopigmented, and height, weight, and head circumference were within the normal range for his age. The implications of these features are discussed in the context of previous work describing a milder phenotype in nondeletion cases of angelman syndrome and work that has examined the prevalence of autism spectrum disorders amongst individuals with angelman syndrome.- - - - - - - - - - ranking = 1keywords = chromosome (Clic here for more details about this article) |
3/17. Characterization of the first supernumerary tricentric ring chromosome 1 mosaicism by conventional and molecular cytogenetic techniques.We report on the conventional cytogenetic and fluorescence in situ hybridization (FISH) results obtained for a 3.5-year-old girl with developmental and language delay and a supernumerary ring chromosome mosaicism in 8% of t-lymphocytes analyzed. Using different conventional and molecular cytogenetic techniques as YAC hybridization and comparative genomic hybridization, we could show that the extra tricentric ring chromosome consists of three heterochromatic blocks with inserted euchromatic material. Additionally, chromosome microdissection followed by FISH analysis demonstrated that the small tricentric ring chromosome consisted of material from the pericentromeric region of chromosome 1q21. Thus, the patient has a mosaic of normal cells and cells with partial pentasomy of the pericentromeric region of chromosome 1. So far, 19 cases with single supernumerary marker chromosome 1 have been published, but no tricentric ring chromosome 1 is, to our knowledge, reviewed in the literature. In this study, we compare the clinical features of our patient with cytogenetically comparable cases described in the literature. We introduce a hypothesis for the formation of a tricentric ring chromosome: starting with a monocentric ring, sister chromatid exchange leading to the formation of a tetracentric ring, which underwent intrastrand recombination generating the tricentric ring.- - - - - - - - - - ranking = 8.6854992174955keywords = chromosome, ring chromosome (Clic here for more details about this article) |
4/17. Chromosome 22q11.2 microdeletion in a patient with hemophilia a.We report a 6-year-old patient with hemophilia a, who also exhibited clinical features typical of 22q11.2 deletion syndrome (22qDS). The specific traits were mild mental retardation, speech delay, hypernasal speech, deficits in voice quality and articulation, narrow palpebral fissures, broad and depressed nasal root, high-arched palate, microstomia, and overfolded ears. The patient had no associated congenital cardiac or palatal malformations. It can be particularly difficult to identify this syndrome in newborns and infants without congenital heart defects. This case underlines that microdeletion of chromosome 22q11.2 should be considered in any patient who exhibits typical clinical features of 22qDS, regardless of whether they have another single-gene disorder.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
5/17. 22q13 deletion syndrome with central diabetes insipidus: a previously unreported association.We describe a two-year-old girl with 22q13 deletion syndrome (MIM # 606232), 46, XX, de l (22) (q13.31). ish del (22) (q13.31) (TUPLE 1 ,ARSA-). The patient has hypotonia, normal growth, severe expressive language delay, mild mental retardation, and minor dysmorphic facial features. In addition, she had central diabetes insipidus that was diagnosed at age two days and resolved at age 27 months. To our knowledge, this association has not been reported previously. Infants with hypotonia, or those suspected to have this syndrome should have high-resolution chromosome analysis and fluorescent in situ hybridization (FISH) studies or molecular analysis, since the chromosomal deletion may be subtle and may go undetected on routine cytogenetic studies. The association of 22q13 deletion syndrome with central diabetes insipidus is reported for the first time.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
6/17. A familial complex chromosome translocation resulting in duplication of 6p25.We report on a girl with psychomotor retardation, severe speech developmental delay and mild dysmorphic features. Molecular cytogenetic analysis showed that the patient was carrier of an insertion (6)(p22.5-->22.4) in chromosome 12. Analysis of the chromosomes of the mother revealed the presence of a complex chromosomal rearrangement. In addition to the insertion (6)(p22.5-->22.4) in chromosome 12 and a pericentric inversion in chromosome 12, the 6p subtelomeric region was absent in the mother. This is, to our knowledge, the smallest pure duplication of chromosome 6p as well as the smallest cryptic subtelomeric 6pter deletion thus far reported.- - - - - - - - - - ranking = 4.5keywords = chromosome (Clic here for more details about this article) |
7/17. Supernumerary ring chromosome 7 mosaicism: case report, investigation of the gene content, and delineation of the phenotype.We report a girl with severe retardation of expressive speech development carrying a small, supernumerary ring chromosome derived from the proximal region of the long arm of chromosome 7. The r(7) chromosome is present in 50% of lymphocytes. We also review the six additional cases with a supernumerary r(7) chromosome reported in the literature. Among these patients, a severe retardation of productive language capabilities is seen as a shared clinical feature, irrespective of the degree of mosaicism as detected in blood. The dysmorphisms in these patients are minor and no shared congenital abnormalities seen. We, therefore, recommend chromosomal investigations in children with unexplained, disproportionately retarded expressive speech performance. Because speech and language acquisition are subject to genetic influences, we investigated whether there are genes on the r(7) chromosome that may affect brain development or function in a dosage-dependent manner. We found that both in our patient and in four patients described by others, the supernumerary r(7) chromosome contains the region from the centromere up to marker D7S613 located at 7q11.23. We speculate that the effects on speech acquisition are mediated by the supernumerary copies of the STX1A and LIMK1 genes, which are both located in this region and known to suppress neurite growth when overexpressed in vitro.- - - - - - - - - - ranking = 6.2141662319419keywords = chromosome, ring chromosome (Clic here for more details about this article) |
8/17. Array CGH detection of a cryptic deletion in a complex chromosome rearrangement.Balanced complex chromosome rearrangements (CCR) are extremely rare in humans. They are usually ascertained either by abnormal phenotype or reproductive failure in carriers. These abnormalities are attributed to disruption of genes at the breakpoints, position effect or cryptic imbalances in the genome. However, little is known about possible imbalances at the junction points. We report here a patient with a CCR involving three chromosomes (2;10;11) and eight breakpoints. The patient presented with behavioural problems as the sole phenotypic abnormality. The rearrangement, which is apparently balanced in G-banding and multicolour FISH, was shown by genomic array analysis to include a deletion of 0.15-1.5 Mb associated with one of the breakpoints. To explain the formation of this rearrangement through the smallest possible number of breakage-and-reunion events, one has to assume that the breaks have not occurred simultaneously, but in a temporal order within the span of a single cell division. We demonstrate that array comparative genomic hybridisation (CGH) is a useful complementary tool to cytogenetic analysis for detecting and mapping cryptic imbalances associated with chromosome rearrangement.- - - - - - - - - - ranking = 3.5keywords = chromosome (Clic here for more details about this article) |
9/17. Molecular characterisation of patients with subtelomeric 22q abnormalities using chromosome specific array-based comparative genomic hybridisation.The 22q13 deletion syndrome is associated with global developmental delay, absent or delayed speech, and generalised hypotonia. In this study, the size and nature of 22q13 deletions (n=9) were studied in detail by high-resolution chromosome specific array-based comparative genomic hybridisation (array CGH). The deletion sizes varied considerably between the different patients, that is, the largest deletion spanning 8.4 Mb with the breakpoint mapping to 22q13.2 and the smallest deletion spanning 3.3 Mb with the breakpoint mapping to 22q13.31. In one case, a unique subtelomeric 3.9 Mb deletion associated with a 2.0 Mb duplication of 22q13 was observed, adding to a growing number of similar cases identified for other chromosome ends. Remarkably, this patient had signs suggestive of retinitis pigmentosa, which has never been reported before in the 22q13 deletion syndrome. The identification of two pairs of recurrent proximal breakpoints on 22q13 suggests that these specific regions may be prone to recombination, due to yet unknown genome architectural features. In addition to the copy number changes on 22q13, a duplication of approximately 330 kb on 22q11.1 was observed and shown to be a genetic large-scale copy number variation without clinical consequences. The current study failed to reveal relationships between the clinical features and the deletion sizes. Global developmental delay and absent or severely delayed speech were observed in all patients, whereas hypotonia was present in 89% of the cases (8/9). This study underscores the utility of array CGH for characterising the size and nature of subtelomeric deletions, such as monosomy 22q13, and underlines the considerable variability in deletion size in the 22q13 deletion syndrome regardless of the clinical phenotype.- - - - - - - - - - ranking = 3keywords = chromosome (Clic here for more details about this article) |
10/17. 47,XXX: what is the prognosis?Eleven unselected 47,XXX girls, now 15 to 22 years of age, have been observed from birth in a prospective study of children with sex chromosome anomalies. A description of their growth and development is presented. The 47,XXX infants were not generally distinguishable from chromosomally normal children in the first year of life, even though there was a slight delay in neuromotor development. By 2 years of age, developmental delays in speech and language often became evident, and speech therapy was often necessitated in the preschool years. Early school problems included speech and language deficiencies, lack of coordination, poor academic performance, and immature behavior; these persisted throughout the school years. By high school age, a 47,XXX girl was generally tall and often subject to somatic complaints. sexual development was generally normal. Seven of the 11 propositae had a diagnosed psychiatric disorder or disturbance at some time during adolescence. Variability within this syndrome is great; one proposita is in college and another is mentally retarded. The frequency of the diagnosis of the 47,XXX karyotype by genetic amniocentesis is estimated to be 1/1000, the same incidence as in the newborn population. Expectant parents must be counseled as to the significance of this karyotype and prognostic information must be given. Suggested guidelines are included.- - - - - - - - - - ranking = 0.5keywords = chromosome (Clic here for more details about this article) |
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