1/11. Phenotypic variability of the cat eye syndrome. Case report and review of the literature.We present a male infant with preauricular skin tags and pits, downslanting palpebral fissures, hypertelorism, ectopic anus, hypospadias, and hypoplastic left heart syndrome. The clinical features in our patient show phenotypic overlap with the cat eye syndrome, as illustrated by the review of 105 reported cases. cytogenetic analysis revealed a supernumerary marker chromosome, which was identified by microdissection and fluorescence in situ hybridization as an isodicentric chromosome 22(pter --> q11.2::q11.2 --> pter). It was proved with probes specific for the cat eye syndrome critical region that this region was present in quadruplicate in the propositus. We conclude that CES is characterized by large phenotypic variability, ranging from near normal to severe malformations, as reflected in the neurodevelopmental outcome. Preauricular skin tags and/or pits are the most consistent features, and suggest the presence of a supernumerary bisatellited marker chromosome 22 derived from duplication of the CES critical region.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/11. parietal bone agenesis and associated multiple congenital anomalies.Congenital defects of the calvaria in general and the parietal bones in particular are rare diseases. The latter are of three kinds: 1) cranioschisis, 2) craniodysostosis, and 3) foramina parietalia permagna (FPP). Here, we describe an exceptional anomaly, namely, complete absence of one parietal bone and dysplasia of the other. Agenesis has been reported twice before in the literature. In these cases, the calvarial defect was the only congenital anomaly. In contrast, the patient described in this article exhibited many other congenital deformities, namely, iris coloboma, facial dysmorphism, a large ventricular septal defect of the heart, and a horseshoe kidney. Some of these deformities are associated with neural crest development. Chromosomal analysis was normal in both blood and fibroblasts, and fluorescent in situ hybridization analysis failed to demonstrate a 22q11 deletion as seen in digeorge syndrome, a neural crest-related disease complex. Since 2000, the third group of congenital defects of the parietal bones, FPP, has been associated with mutations of the MSX-2 gene. In our case, a genetic analysis of this gene was performed, but no mutations or deletions of MSX-2 were detected.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/11. Ocular coloboma and high myopia with hirschsprung disease associated with a novel ZFHX1B missense mutation and trisomy 21.Syndromic hirschsprung disease has been associated with mutations in ZFHX1B, a Smad-interacting transcriptional repressor protein. Tissue in situ hybridization has demonstrated strong expression of ZFHX1B in the developing eye, suggesting that some mutations in this gene may cause visual loss. However, none of the reported mutations have been associated with an ocular phenotype. We describe a patient with down syndrome and hirschsprung disease with high myopia and ocular coloboma affecting the iris and retina. In addition to trisomy 21, a novel, de novo heterozygous A to G transition in exon 8 of the ZFHX1B gene was identified, which results in a R953G amino acid substitution. This abnormality was not seen in a screen of 200 chromosomes from ethnically matched, normal controls. The arginine residue at position 953 is an extremely conserved amino acid throughout evolution. This is the first report associating hirschsprung disease and severe eye defects with a specific genetic mutation and is the first report of a mutation in ZFHX1B causing a developmental ocular anomaly.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/11. A new case of a severe clinical phenotype of the cat-eye syndrome.A new case of severe clinical phenotype of the cat-eye syndrome: We report on a female infant with severe clinical phenotype of Cat-eye Syndrome (CES). At birth, she had respiratory distress and marked hypotonia. physical examination showed major craniofacial anomalies including microcephaly, bilateral total absence of the external ears, hypertelorism, bilateral ocular coloboma of iris and micrognathia. In addition, she had anal stenosis, a patent ductus arteriosus and intra- and extra- hepatic biliary atresia. She deteriorated with the development of bradycardia. She died at age one month of cardiac failure. cytogenetic analysis of the proband showed an extra de novo small bisatelllited marker chromosome in all cells examined. Molecular cytogenetic analysis with fluorescence in situ hybridization (FISH) identified the marker as a CES chromosome. Thus, the patient's karyotype was: 47, XX, idic(22)(pter-->q11.2 ::q11.2-->pter). The duplication breakpoints giving rise to the CES chromosome were distal to the digeorge syndrome (DGS) locus 22q11.2. The marker could be classed as a type 11 symmetrical (10). According to a recent review of CES literature (1) only 41 % of the CES patients have the combination of iris coloboma, anal anomalies and preauricular anomalies. Almost 60% are hard to recognize by their phenotype alone. Only twelve patients showed a severe clinical phenotype leading to the death of the child. This phenotypic variability increases the difficulties of genetic counseling.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/11. FISH approach to determine cat eye syndrome chromosome breakpoints of a patient with cat eye syndrome type II.We report a 19-year-old man with craniofacial dysmorphic features, anorectal malformations, eye colobomas, orthopaedic anomalies, and mild neurodevelopmental delay. Cat eye syndrome (CES) was suspected, and confirmed by cytogenetic analysis which showed the presence of a supernumerary bisatellited chromosome, identified by fluorescence in situ hybridization (FISH) as invdup(22). The marker was further analyzed with six BAC clones located at the 22q11.1 and 22q11.2 regions; this analysis allowed correct assignment at low copy repeat 4 on chromosome 22 (LCR22-4) of the two breakpoints, confirming the presence of a CES chromosome type II. The patient's phenotype is considered in the light of the cytogenetic, and FISH investigations results and other patients reported in literature. Molecular definition of the breakpoints at the LCR22-4 copy confirms the role of different chromosome 22-specific LCRs in CES chromosomes generation, as well as in other chromosome 22 germ line rearrangements. Our report confirms that, unlike other conditions, i.e. the invdup(15) bisatellited dicentric marker, the CES phenotype does not appear to correlate with the size of the marker chromosome. Additional cases are necessary to be able to draw more specific genotype-phenotype correlations and to determine the outcome of patients with CES, especially when this rare condition is diagnosed in prenatal age.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/11. 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) |
7/11. Parental origin of the extra chromosome in the cat eye syndrome: evidence from heteromorphism and in situ hybridization analysis.Two individuals, a boy and girl, with a clinical diagnosis of cat eye syndrome had an extra bisatellited chromosome. In the girl, the diagnosis was made on the basis of coloboma of the right iris, right preauricular pit, and imperforate anus; in the boy, bilateral colobomata of the iris, down-slanting palpebral fissures, right preauricular skin tag, and right preauricular pit. Multiple staining techniques were used to characterize the extra chromosomes. With G-banding the extra chromosome usually appeared monocentric with two major G-positive bands, but with satellites on both ends; with C-banding, two C-band positive regions were evident, indicating that the chromosomes were likely dicentric. silver staining demonstrated the presence of NORs near each end; Q-banding showed satellites on each end, differing in brightness and size. The chromosomes of the parents were normal; comparisons of Q-band heteromorphisms of the acrocentric chromosomes of the parents with those of the extra chromosome showed in each case one short arm/satellite region of the extra chromosome identical in appearance to one chromosome 22 of the mother and the other end of the extra bisatellited chromosome identical to the short arm/satellite of the mother's second chromosome 22. This extra chromosome, then, is the result of a maternal meiotic error in each case. in situ hybridization studies using the chromosome 22-derived probe p22/34, which identifies locus D22S9, showed 16% of the cells from the female patient to have silver grains on the proximal long arm of the normal chromosome 22 and 14% on the extra chromosome, while 10% of cells from the male had grains on the normal chromosomes 22 and an equal number on the extra chromosome, confirming the chromosome 22 origin of the extra chromosome in these patients.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
8/11. Maternal derivation of inv dup (22) and clinical variation in cat-eye syndrome.cytogenetic analysis in a male child with dismorphies and renal anomalies showed an extra bisatellited chromosome. in situ hybridization and an analysis of cytogenetic polymorphisms revealed that the abnormal chromosome derived from a single maternal chromosome 22.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/11. prenatal diagnosis of the derivative chromosome 22 associated with cat eye syndrome by fluorescence in situ hybridization.Cytogenetic studies of cultured amniocytes demonstrated a karyotype of 46,XX/47,XX, mar. A bisatellited, dicentric, distamycin-DAPI negative, NOR-positive marker was present in 76 per cent of the metaphases examined. Similar markers have been associated with cat eye syndrome (CES). We report on the utilization of fluorescence in situ hybridization (FISH) with a 14/22 alpha-satellite probe and a chromosome 22-specific cosmid for locus D22S9 to determine the origin of the prenatally detected supernumerary marker chromosome. FISH studies demonstrated that the marker is a derivative of chromosome 22 and enabled us to provide the family with additional prognostic information.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
10/11. Limb anomalies in DiGeorge and CHARGE syndromes.Limb anomalies are not common in the DiGeorge or CHARGE syndromes. We describe limb anomalies in two children, one with DiGeorge and the other with charge syndrome. Our first patient had a bifid left thumb, tetralogy of fallot, absent thymus, right facial palsy, and a reduced number of T-cells. A deletion of 22q11 was detected by fluorescence in situ hybridization (FISH). The second patient, with charge syndrome, had asymmetric findings that included right fifth finger clinodactyly, camptodactyly, tibial hemimelia and dimpling, and severe club-foot. The expanded spectrum of the DiGeorge and CHARGE syndromes includes limb anomalies.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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