1/26. Submicroscopic deletion in cousins with prader-willi syndrome causes a grandmatrilineal inheritance pattern: effects of imprinting.The prader-willi syndrome (PWS) critical region on 15q11-q13 is subject to imprinting. PWS becomes apparent when genes on the paternally inherited chromosome are not expressed. Familial PWS is rare. We report on a family in which a male and a female paternal first cousin both have PWS with cytogenetically normal karyotypes. fluorescence in situ hybridization (FISH) analysis shows a submicroscopic deletion of SNRPN, but not the closely associated loci D15S10, D15S11, D15S63, and GABRB3. The cousins' fathers and two paternal aunts have the same deletion and are clinically normal. The grandmother of the cousins is deceased and not available for study, and their grandfather is not deleted for SNRPN. dna methylation analysis of D15S63 is consistent with an abnormality of the imprinting center associated with PWS. "Grandmatrilineal" inheritance occurs when a woman with deletion of an imprinted, paternally expressed gene is at risk of having affected grandchildren through her sons. In this case, PWS does not become evident as long as the deletion is passed through the matrilineal line. This represents a unique inheritance pattern due to imprinting.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/26. fluorescence in situ hybridization detectable mosaicism for angelman syndrome with biparental methylation.We present a child with mild to moderate global developmental delay including severe speech impairment, inappropriate happy demeanor, wide-based gait, frequent ear infections with mild hearing loss, deep-set eyes, a wide mouth, widely-spaced teeth, normal head circumference, and no seizures. Results of peripheral blood lymphocyte chromosomal analysis with GTG banding were normal. However, fluorescence in situ hybridization (FISH) studies showed mosaicism for a deletion of probes (D15S10 and SNRPN) from the angelman syndrome (AS) critical region with approximately 40% of peripheral lymphocytes having the deletion. The deleted chromosome 15 also showed centromeric duplication, which was detected with a D15Z1 probe [46,XX, dic(15)(pter-->q11.1::p11.2-->q11. 1::q13-->qter)]. The same duplication pattern was observed in 30% of the nuclei obtained from a buccal smear. Methylation studies using polymerase chain reaction with sodium bisulfite-treated DNA demonstrated a normal biparental methylation pattern. To the best of our knowledge, this is the first case with AS and a FISH detectable deletion in a mosaic pattern. We recommend FISH studies for the detection of mosaicism in the patients with AS clinical findings even if results of the methylation studies are normal.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
3/26. congenital hypothyroidism with prader-willi syndrome.We report a 1 year-old female patient with severe hypotonia who has congenital hypothyroidism and prader-willi syndrome (PWS). At birth she was found to have congenital hypothyroidism caused by an ectopic sublingual thyroid gland and was commenced on thyroid replacement therapy. She continued to have severe motor delay and therefore further diagnostic evaluation was performed. PWS was confirmed by DNA and fluorescence in situ hybridization (FISH) analysis. This report emphasizes the need to further investigate patients who are found to have congenital hypothyroidism and do not improve adequately on treatment.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/26. Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman syndrome but not prader-willi syndrome.angelman syndrome (AS) is a disorder of psychomotor development caused by loss of function of the imprinted UBE3A gene. Since the paternal UBE3A copy is regularly silent, only mutations inactivating the maternal copy cause AS. Among 1,272 patients suspected of AS, we found one with an isolated deletion of the UBE3A gene on the maternally inherited chromosome. Initial dna methylation testing at the SNURF-SNRPN locus in the patient revealed a normal pattern. The deletion was only detected through allelic loss at microsatellite loci D15S1506, D15S122, and D15S210, and confirmed with fluorescence in situ hybridization (FISH) using bacterial artificial chromosome (BAC) probes derived from the loci. It extends approximately 570 kilobase pairs (kbp), encompassing the UBE3A locus, and is flanked by loci PAR/SN and D15S986. The deletion is familial, and haplotype studies suggest that a great grandfather of the index patient already carried this deletion, and that it causes AS when inherited through the female germline but not prader-willi syndrome (PWS) when paternally inherited. Our findings support the hypothesis that the functional loss of maternal UBE3A gene activity is sufficient to cause AS and that the deleted region does not contain genes or other structures that are involved in PWS. Finally, this case highlights that methylation tests can fail to detect some familial AS cases with a recurrence risk of 50%.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/26. Low level of mosaicism in atypical Prader Willi syndrome: detection using fluorescent in situ hybridization.Prader Willi syndrome (PWS) most commonly is due to paternal micro-deletion of 15q11-q13. Although PWS is not a rare condition, mosaic micro-deletion cases are reported rarely. FISH using PWS micro-deletion probe is the most useful method to detect deletion including mosaicism. In this report we describe a female child with clinical features of atypical PWS and FISH analysis showing mosaicism for deletion in the PWS critical region. This is first mosaic deletion case of PWS from Indian subcontinent.- - - - - - - - - - ranking = 4keywords = hybridization (Clic here for more details about this article) |
6/26. Molecular characterization of a unique de novo 15q deletion associated with prader-willi syndrome and central visual impairment.We report a 2-year-old boy with prader-willi syndrome (PWS) caused by a deletion of the PWS critical region as a result of an unbalanced translocation t(3;15). Additional features, including central visual impairment, relative macrocephaly, retrognathia, preauricular tags, and bilateral club-feet, were noticed. The extension of the deletion was determined by fluorescence in situ hybridization (FISH) analysis using 11 region-specific YAC clones. Nine YACs were found to be deleted, allowing us to determine that the deletion is larger than in patients with typical PWS deletions. The karyotype of this patient can thus be designated: 45,XY,-15,der(3)t(3;15)(qter;q14).ish der(3)t(3;15)(qter;q14) (wcp3 ,wcp15 ,D15S10-,PML ,D15Z1-,D3S4560 ,801_f_9x1, 815_e_6x2) de novo. Molecular analyses using seven polymorphic markers helped to narrow down the breakpoint between marker ACTC.PC3 and the distal end of the YAC 815_e_6. These results provide evidence that haploinsufficiency for genes in 15q13-q14, not affected in common PWS deletions, is associated with the additional features found in the patient, including a central visual impairment.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/26. Partial hexasomy of chromosome 15.Marker chromosomes originating from chromosome 15, often referred to as inv dup(15), is the most common marker chromosome found in humans. The large marker 15 that contains the prader-willi syndrome (PWS)/angelman syndrome (AS) chromosome region is usually associated with an abnormal phenotype of moderate to severe mental retardation, seizures, poor motor coordination, behavioral problems, and mild dysmorphic features. We report here an infant boy with two copies of the large inv dup(15). A 10-day-old infant was found to have infantile spasms, microcephaly, hypotonia, and lethargy. Lymphocyte chromosome analysis revealed a 48,XY, 2mar karyotype. fluorescence in situ hybridization with probes rRNA, D15Z4, D15S11, and GABRB3 demonstrated that both markers were chromosome 15 in origin and contained the Prader-Willi/angelman syndrome chromosome region. Therefore, this patient is hexasomic for the PWS/AS region. The phenotype of this patient does not appear to be significantly more severe than patients with one copy of the large inv dup(15) at birth, however, follow-up evaluation of the patient at 21 months of age shows that this patient has frequent and severe seizure activity, severe bilateral hearing loss, and cortical blindness.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/26. Deletion of chromosome 15pter-->q11.2 due to t(Y;15) in a boy with prader-willi syndrome.Chromosome analysis of lymphocytes from a patient with the clinical presentation of prader-willi syndrome showed the presence of 45 chromosomes, including a der(Y) resulting from an unbalanced t(Y;15)(q12;q11.2). in situ hybridization using DYZ3 and DYZ2 showed positive signals at the paracentromeric region on the short arm and at the heterochromatic region of the long arm of the y chromosome, respectively. The prader-willi syndrome in this patient is caused by the deficiency of a very small region involving 15cen-->q11.2.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/26. prader-willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic hybridization.prader-willi syndrome (PWS) is caused by lack of expression of paternally inherited genes on chromosome 15q11-->15q13. Most cases result from microdeletions in proximal chromosome 15q. The remainder results from maternal uniparental disomy of chromosome 15, imprinting center defects, and rarely from balanced or unbalanced chromosome rearrangements involving chromosome 15. We report a patient with multiple congenital anomalies, including craniofacial dysmorphology, microcephaly, bilateral cryptorchidism, and developmental delay. cytogenetic analysis showed a de novo 45,XY,der(5)t(5;15)(p15.2;q13), -15 karyotype. In effect, the proband had monosomies of 5p15.2-->pter and 15pter-->15q13. Methylation polymerase chain reaction analysis of the promoter region of the SNRPN gene showed only the maternal allele, consistent with the PWS phenotype. The proband's expanded phenotype was similar to other patients who have PWS as a result of unbalanced translocations and likely reflects the contribution of the associated monosomy. Array comparative genomic hybridization (array CGH) confirmed deletions of both distal 5p and proximal 15q and provided more accurate information as to the size of the deletions and the molecular breakpoints. This case illustrates the utility of array CGH in characterizing complex constitutional structural chromosome abnormalities at the molecular level.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
10/26. Maternal uniparental disomy in a patient with prader-willi syndrome with an additional small inv dup(15) chromosome.prader-willi syndrome (PWS) is a complex genetic disorder. About 70% of cases have a paternal deletion at 15q11-q13, and most of the remaining cases are caused by maternal uniparental disomy (UPD). In rare cases of PWS with maternal UPD, small marker chromosomes are identified. patients with inv dup(15) are at an increased risk of developing PWS or angelman syndrome (AS) due to UPD. They may be also at increased risk for developmental delay due to additional copies of genes located within the PWS/AS critical region. Therefore, molecular investigations in patients with a supernumerary marker chromosome (SMC) are necessary to provide proper genetic counseling. We report a female infant with central hypotonia, weak crying, feeding problems, failure to thrive, and developmental delay after birth. Chromosome analysis revealed an SMC in 55% of metaphase cells. fluorescence in situ hybridization showed that this marker chromosome was constituted by a small isodicentric inverted duplication of chromosome 15 [inv dup(15)]. Microsatellite analysis showed uniparental isodisomy of maternal chromosome 15 in the proband. diagnosis of PWS was further confirmed by methylation-specific polymerase chain reaction. The inv dup(15) marker chromosome was also of maternal origin. Follow-up at the age of 18 months revealed a height in the 10th percentile and weight in the 50th percentile. She had poor activity and muscle tone, and was unable to walk independently. There was no psychomotor retardation, behavior disturbance or seizure.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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