1/7. trisomy 4q syndrome: presentation of a new case and review of the literature.We describe the 11th case of a de novo partial trisomy of the long arm of chromosome 4, with the extra segment spanning from 4q27 to 4q35. The aberration resulted from an unbalanced translocation of material from 4q to the short arm of chromosome 7, as evident from fluorescent in situ hybridization. Microsatellite analysis revealed the extra material to originate from the father. The karyotype was interpreted as 46,XX,der(7)t(4;7)(q27;p22). The patient is a 13-year-old girl with severe mental retardation, growth retardation, hearing impairment as well as minor foot, thumb and facial anomalies. Although the extent of the aberration varies between the reported patients, there are nevertheless features in common, suggestive of a trisomy 4q syndrome. The clinical findings most frequently reported are: mental retardation, seizures, microcephaly, hearing impairment and growth retardation, as well as epicanthic folds, high/broad/depressed nasal bridge, malformed ears, tooth and thumb anomalies. Almost the entire long arm of chromosome 4, except band q11, has been involved in trisomies/duplications, but 4q27 and 4q31 seem to be preferentially engaged in the trisomy 4q syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/7. Molecular characterization of a 12q22-q24 deletion associated with congenital deafness: confirmation and refinement of the DFNA25 locus.The DFNA25 locus for autosomal dominant nonsyndromic hereditary hearing loss has been mapped to 12q21-q24 by linkage analysis. A de novo deletion in a six-year-old boy with congenital hearing loss as well as mental and motor retardation now provides independent confirmation of this genetic localization and narrows the critical interval to 13 cM in the 12q22-q24.1 region. Mapping of the deletion was performed using fluorescence in situ hybridization (FISH) analysis with region-specific yeast artificial chromosome (YAC) clones. Ten YACs 929_e_4, 959_c_3, 746_h_7, 817_h_10, 886_a_6, 916_h_9, 969_c_12, 747_e_2, 812_h_12, and 959_f_8 were absent from one chromosome 12 from the patient. Molecular analyses of eight polymorphic markers helped to narrow down the breakpoints and demonstrated that the derivative chromosome 12 is of paternal origin. Several known genes including ATP2A2, UBE3B, and VR-OAC that map in the 12q22-q24.1 region are included in the deletion. These results provide evidence that haploinsufficiency for a gene or genes in 12q22-q24.1 is associated with autosomal dominant deafness.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/7. Different tissue distribution of a mitochondrial dna duplication and the corresponding deletion in a patient with a mild mitochondrial encephalomyopathy: deletion in muscle, duplication in blood.Large-scale heteroplasmic mtDNA rearrangements were identified in a 57-year-old woman with chronic depressive disorder, hearing-loss, diabetes mellitus and a slowly progressive encephalomyopathy. A high percentage of a 24.2 kb duplicated molecule was found in lymphocytes whereas the corresponding deletion dimer dominated in muscle. PCR and Southern blot analyses were used to identify a 7658 bp duplication/deletion fragment. The duplicated mtDNA disrupted the cytochrome oxidase subunit I and cytochrome b genes at a position where there were no direct repeats. Duplicated mtDNA was not observed in the mother and brother of the patient. Histochemical analysis of skeletal muscle demonstrated pathological accumulation of mitochondria in cytochrome c oxidase negative fibers. in situ hybridization demonstrated only deleted mtDNA in cytochrome c oxidase negative fibres. We conclude that occurrence of deleted mtDNA correlates with phenotypic expression and that the duplicated mtDNA might serve as a generator of deletions, but is not directly pathogenic.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/7. phenotype-genotype correlation in two patients with 12q proximal deletion.Proximal 12q deletion is a very rare chromosomal abnormality. Only five cases have been reported. Among the five, an Argentinian patient (Case 1) with del(12)(q11q13) and a Japanese patient (Case 2) with del(12)(q12q13.12) were analyzed because they shared several clinical features: growth and psychomotor developmental delay; strabismus; broad and short nose with anteverted nostrils; high, arched palate; large, lowset ears; widely set nipples; short fingers and clinodactyly of fifth fingers; and abnormality of the second and third toes. To clarify the correlation between the deleted genes and their phenotypes, we delimited their deleted regions by fluorescence in situ hybridization (FISH). The overlapped region in the deletions spanned 6.2 Mb where at least 15 genes were predicted to localize on the current human genome database. Among them, YAF2 and AMIGO2 were the most plausible candidates to affect growth and psychomotor retardation, respectively, in both cases. Regarding unique symptoms in each case, congenital fibrosis of the extraocular muscles found only in Case 1 may be caused by KIF21A deletion and hearing loss and cleft palate in Case 2 by COL2A1 defect.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/7. Subtelomeric 6p deletion: clinical, FISH, and array CGH characterization of two cases.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.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
6/7. Pallister-Killian syndrome: a mild case diagnosed by fluorescence in situ hybridization. review of the literature and expansion of the phenotype.Pallister-Killian syndrome (PKS) is a rare disorder characterized by a specific combination of anomalies, mental retardation and mosaic presence of a supernumerary isochromosome 12p which is tissue-limited. We report an atypical case of PKS with a mild phenotype. Flourescence in situ hybridization (FISH) was used to demonstrate that the supernumerary marker chromosome identified in the patient's fibroblasts was an isochromosome 12p. This study broadens the spectrum of PKS phenotype. It also illustrates the usefulness of fluorescence in situ hybridization in diagnosis of patients with chromosomal abnormalities and mild or atypical clinical findings.- - - - - - - - - - ranking = 6keywords = hybridization (Clic here for more details about this article) |
7/7. Submicroscopic deletion in 14q32.3 through a de novo tandem translocation between 14q and 21p.We describe a male child with craniofacial anomalies, postnatal onset growth retardation, microcephaly, multiple minor anomalies, hearing loss, and moderate delay of mental and statomotor development. He carries a previously undescribed tandem translocation between the long arm of chromosome 14 and the short arm of chromosome 21 that arose de novo. As proven by fluorescence in situ hybridization a microdeletion not detectable with high-resolution G-banding occured in 14q32.3, the terminal band on the long arm of chromosome 14. The resulting phenotype includes most abnormalities encountered in patients with terminal 14q32.3 deletions but in addition includes some characteristics of the ring chromosome 14 syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |