1/14. Novel assay for Roberts syndrome assigns variable phenotypes to one complementation group.Roberts syndrome (RS) is a rare autosomal recessive disorder characterized by heterogeneous clinical features, the most notable being tetraphocomelia, cleft lip, and cleft palate. cells derived from most RS patients exhibit abnormal cytogenetic and cellular phenotypes that include the premature separation of para- and pericentromeric heterochromatin visible on C-banded metaphase chromosomes, a phenomenon referred to as heterochromatic splaying. Previously, it was shown that these abnormal phenotypes can be complemented following somatic cell hybridization between RS cells and control cells. In the current study, a permanent cell line was established from a new RS patient with a more severe phenotype than represented by previously established cells in culture. With a newly developed assay designed to facilitate rapid evaluation of in vitro complementation, we assigned this new patient to the same genetic complementation group defined by other, less severely affected patients. The results demonstrate that a single complementation group defines RS patients with heterochromatic splaying regardless of clinical severity.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/14. 4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.Chromosome 4p- syndrome is a multiple malformation syndrome associated with partial deletion of the short arm of chromosome 4 (4p-). It is characterized by dysmorphic features and retarded development. cleft lip and/or palate are the major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the principal clinical manifestations of this condition are characteristic craniofacial abnormalities, generalized hypotonia and severe mental retardation. We present the first case of a female infant with 4p deletion and tetrasomy 9p mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. karyotype analysis of lymphocytes cultured from the patient revealed that she was mosaic: 86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4) (p15.32), idic (9)(q12). The G-banding pattern appeared consistent with either translocation or partial proximal deletion of 4p. In order to make a definitive cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg, her cleft lip was repaired. Before and after surgery there were no seizures, and the postoperative course was uneventful.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/14. Misclassification risk of patients with bilateral cleft lip and palate and manifestations of median facial dysplasia: A new variant of del(22q11.2) syndrome?The generic term median facial dysplasia (MFD) describes a subgroup of patients with cleft lip and palate exhibiting characteristic craniofacial defects: (1) short prolabium, (2) absence of frenulum labii, (3) hypoplasia of premaxilla, (4) absent upper central and lateral incisors of the cleft side, and (5) deficient septal cartilage and nasal spine. Gross brain malformations are usually absent in MFD. The same craniofacial malformations are also described in patients with holoprosencephaly sequence (HPE-S). We report on two male patients with bilateral cleft lip and palate showing the facial findings of MFD or HPE-S. Additional congenital malformations were anal atresia in one patient and severe cardiac defect in the other. In both, HPE was excluded by brain imaging, although uncommon brain anomalies were detected consisting of multiple white-matter lesions in the one patient and unusual enlargement and tortuosity of intracerebral blood vessels in both patients. In addition to facial anomalies, the patients also had psychiatric problems typically seen in velo-cardio-facial syndrome (VCFS). fluorescence in situ hybridization (FISH) analysis confirmed a 22q11.2 microdeletion in both.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/14. Van der Woude syndrome with sensorineural hearing loss, large craniofacial sinuses, dental pulp stones, and minor limb anomalies: report of a four-generation Thai family.A four-generation Thai family affected with Van der Woude syndrome is reported. The disorder appeared to be originally inherited from a person who was half Thai and half Pakistani. The lip lesions found in this family were varied and did not appear to be related to other phenotypes. There were some clinical manifestations possibly specific for the condition in this family. They included sensorineural hearing loss, prominent frontal bone, large frontal/sphenoidal/maxillary sinuses with increased mastoid air cells, long tooth roots, dental pulp stones, ankyloglossia, brachydactyly of hands, brachyphalangy, and hyperphalangy of toes, and single flexion crease of the fifth fingers. fluorescence in situ hybridization analysis revealed no visible deletion at a 1q32-41 region.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/14. Duplication of (2)(q11.1-q13.2) in a boy with mental retardation and cleft lip and palate: another clefting gene locus on proximal 2q?A 4-year-old boy with left cleft lip and cleft palate, multiple minor anomalies and developmental delay revealed an abnormal chromosome 2 with enlarged proximal long arm, de novo, in his karyotype. fluorescence in situ hybridization with a chromosome 2 library and band-specific YACs confined the duplicated segment to 2q11.1-q13.2 and indicated a direct tandem duplication due to unbalanced crossover between chromatids.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/14. Terminal tandem duplication of 16p: a case with "pure" partial trisomy (16)(pter-->p13).A new-born infant was found to have multiple congenital anomalies Including bilateral cleft of lip and palate, club-hands and feet, and heart defects. High resolution chromosome analysis showed a de novo tandem duplication of the terminal part of the short arm of chromosome 16, resulting in a dup(16)(pter-->p13). Fluorescent in situ hybridization with a chromosome 16-specific paint confirmed that the extra material belonged to chromosome 16.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/14. Identification and characterization of a novel gene disrupted by a pericentric inversion inv(4)(p13.1q21.1) in a family with cleft lip.cleft lip with or without cleft palate is a common birth defect affecting 1 in every 700 live births. Several genetic loci are believed to be involved in the pathogenesis of syndromic and non-syndromic clefting. We identified a pericentric inversion of chromosome 4, inv(4)(p13q21) that segregates with cleft lip in a two-generation family. By using a combination of fluorescence in situ hybridization, yeast artificial chromosome, bacterial artificial chromosome contig mapping, and database searching we mapped and sequenced the inversion breakpoint region. The pericentric inversion disrupts a gene (ACOD4) on chromosome 4q21 that codes for a novel acyl-CoA desaturase enzyme. The 3.0 kb human ACOD4 cDNA spans approximately 170 kb and is composed of five exons of ACOD4. The inversion breakpoint is located in the second exon. The 3.0 kb mRNA is expressed at high level in fetal brain; a lower expression level was found in fetal kidney. No expression of ACOD4 was detected in fetal lung or liver or in adult tissues. The five exons code for a protein of 330 amino acids, with a predicted molecular weight of 37.5 kDa. The protein is highly similar to acyl-CoA desaturases from drosophila melanogaster to Homo sapiens. The catalytically essential histidine clusters and the potential transmembrane domains are well conserved.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/14. association of autosomal dominant cleft lip and palate and translocation 6p23;9q22.3.Orofacial clefting (OFC) is genetically complex in that no single gene defect is responsible for all forms. We have identified a family who exhibit autosomal dominant orofacial clefting together with some features of ectodermal dysplasia. In this family there is concordance between these features and an apparently balanced translocation t(6;9)(p23;q22.3) which raises the possibility that a locus for one form of orofacial clefting may be located at one of the translocation breakpoints. Fluorescent in situ hybridization has shown that a candidate gene for OFC, which maps to distal 6p, is located on the derived chromosome 9 in affected individuals from this family. Further characterization of the translocation breakpoints and of their relationship with the candidate gene will determine whether a gene important for normal facial and/or ectodermal development is disrupted in this family.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/14. Ring chromosome 4 and wolf-hirschhorn syndrome (WHS) in a child with multiple anomalies.We report on a 16-month-old male patient with ring chromosome 4 and deletion of wolf-hirschhorn syndrome (WHS) region with multiple congenital anomalies including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices. Peripheral chromosome analysis of the patient showed 46,XY,r(4)(p16.3q35) de novo. Multicolor fluorescence in situ hybridization (FISH) study was also performed and according to multicolor banding (MCB) a r(4)(::p16.3 --> q34.3 approximately 35.1::) was found in all metaphases. Subtelomeric 4p region, subtelomeric 4q region, as well as, Wolf-Hirschhorn critical region were deleted in ring chromosome 4. Genomic microarray analysis was also performed to delineate the size of deletion. Cranial magnetic resonance imaging (MRI) showed hypoplastic corpus callosum, delayed myelinization, and frontal and occipital lobe atrophies. Both maternal and paternal chromosomal analyses were normal. We compare the phenotypic appearance of our patient with the previously reported 16 cases of ring chromosome 4 in the medical literature.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/14. 10p duplication characterized by fluorescence in situ hybridization.We describe a patient with severe failure to thrive, mild-moderate developmental delay, cleft lip and palate, and other anomalies. Routine cytogenetic analysis documented a de novo chromosome rearrangement involving chromosome 4, but the origin of the derived material was unknown. Using chromosome specific painting probes, the karyotype was defined as 46,XY,der(4) t(4;10)(q35;p11.23). Characterization of the dup(10p) by fluorescence in situ hybridization (FISH) analysis provides another example of the usefulness of this technology in identifying small deletions, duplications, or supernumerary marker chromosomes.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
| | Next -> |