1/4. Interstitial deletion and ring chromosome derived from 19q. Proximal 19q trisomy phenotype.A small supernumerary ring chromosome has been found in a boy with overweight, dysmorphic facies and mental retardation. His mother had an interstitial deletion of the long arm of chromosome 19 and the same ring chromosome. By means of fluorescence in situ hybridization the ring chromosome was shown to be derived from the deleted chromosome, after the occurrence of two breaks: one in the centromere region, the other in the q-arm of chromosome 19.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/4. Elucidation of a cryptic interstitial 7q31.3 deletion in a patient with a language disorder and mild mental retardation by array-CGH.We report on a 14-year-old boy who presented with bilateral cleft lip and palate, hearing loss, a language processing disorder, and mild mental retardation (MR). G-banded chromosome analysis of the patient and his family revealed he carried an apparently balanced de novo complex translocation involving chromosomes 5, 6, and 7. Chromosomal comparative genomic hybridization (CGH) was performed to investigate the possibility of any genomic imbalance as a result of the complex rearrangement. No abnormality was detected at any of the translocation breakpoint regions (5p13.2, 6p24, 7q21.1, and 7q21.3), nor was there any other imbalance which fell inside our significance level of 0.8-1.2. Array-CGH analysis was initiated to perform a higher resolution search for gains and losses, and revealed a deletion of two adjacent clones, CTB-133K23 and RP11-112P4, mapping to 7q31.3, which are 4.4 Mb apart. fluorescence in situ hybridization (FISH) using these two clones confirmed the deletion. 7q31 has frequently been implicated in the search for genes involved in speech and language disorders. The specific 7q31.3 region deleted in our patient has significant overlap with some such areas of the genome. These findings are, therefore, of value in identifying genes involved in the speech and language phenotypes. This study has shown the importance of array-CGH in investigating patients who have clinical features suggestive of a chromosome abnormality, but with apparently balanced chromosome rearrangements. It has demonstrated that the array-CGH technique provides a much greater insight into submicroscopic chromosome imbalances than conventional cytogenetic techniques.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
3/4. Characterization of the phenotype and definition of the deletion in a new patient with ring chromosome 22.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.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/4. Characterization of a novel cation transporter ATPase gene (ATP13A4) interrupted by 3q25-q29 inversion in an individual with language delay.Specific language impairment (SLI) is defined as failure to acquire normal language skills despite adequate intelligence and environmental stimulation. Although SLI disorders are often heritable, the genetic basis is likely to involve a number of risk factors. This study describes a 7-year-old girl carrying an inherited paracentric inversion of the long arm of chromosome 3 [46XX, inv(3)(q25.32-q29)] having clinically defined expressive and receptive language delay. fluorescence in situ hybridization (FISH) with locus-specific bacterial artificial chromosome clones (BACs) as probes was used to characterize the inverted chromosome 3. The proximal and distal inversion breakpoint was found to reside between markers D3S3692/D3S1553 and D3S3590/D3S2305, respectively. ATP13A4, a novel gene coding for a cation-transporting P-type ATPase, was found to be disrupted by the distal breakpoint. The ATP13A4 gene was shown to comprise a 3591-bp transcript encompassing 30 exons spanning 152 kb of the genomic dna. This study discusses the characterization of ATP13A4 and its possible involvement in speech-language disorder.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |