1/6. Molecular and clinical characterization of a patient with duplication of 1p36.3 and metopic synostosis.Chromosome 1p duplications are rare. There have been only 11 reported cases of isolated 1p duplication, all of which were proximal, interstitial duplications. We present a patient with a terminal duplication of 1p (1p36.3). To our knowledge, this is the first such reported case. Our patient presented with metopic synostosis, rectal stenosis, atrial septal defect, and mildly delayed gross motor development. Molecular characterization using microsatellite marker analysis and fluorescence in situ hybridization (FISH) revealed an area of duplication between p58 and D1S2893, approximately 13 cM in size. We compare our patient's clinical findings with the clinical phenotype found in patients with the corresponding deletion of 1p36.3 and discuss the role of gene dosage in other deletion/duplication syndromes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/6. An unusual reciprocal translocation detected by subtelomeric FISH: interstitial and not terminal.An 11-month-old boy with a pattern of dysmorphic signs, an atrial septal defect, right inguinal hernia, bilateral undescended testes, bilateral urinary reflux, right renal dysplasia, and developmental delay had an abnormal chromosome 11 with additional material of unknown origin attached to the long arm in his karyotype. The paternal karyotype was normal 46,XY, while the mother's karyotype was 46,XX,t(2;11)(q35;q24.2). Thus, a reciprocal terminal exchange was assumed resulting in duplication of distal 2q material and a small subterminal 11q deletion. However, application of subtelomeric fluorescence in situ hybridization (FISH) probes indicated that the translocation was not a terminal reciprocal exchange, but was interstitial at least for one of the chromosomes, which would be highly unusual since most interstitial translocations are non-reciprocal. Based on the results of FISH and microsatellite marker examinations, the designation of the breakpoints and thus of the deleted and duplicated segments had to be revised. The findings have implications for karyotype-phenotype correlation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/6. diagnosis of tetrasomy 18p using in situ hybridization of a dna probe to metaphase chromosomes.We identified an isochromosome of 18p [47,XY, i(18p)] conclusively by in situ hybridization of an 18p-specific probe (B74; D18S3) to metaphase chromosomes of an affected patient. Clinical findings included mental retardation, microcephaly, and an atrial septal defect. Although there is similarity to patients previously described with tetrasomy 18p, it is impossible to rule out a low frequency of misdiagnoses in karyotypes determined solely by standard cytogenetic analyses. We expect the ability to conclusively identify an i(18p) to lead to the delineation of tetrasomy 18p as a distinct clinical syndrome.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
4/6. trisomy 16 mosaicism in amniotic fluid cell cultures.trisomy 16 mosaicism was found in amniotic fluid cells in a patient undergoing amniocentesis because of elevated second-trimester maternal serum alpha-fetoprotein (MSAFP) (2.80 MOM), a markedly elevated human chorionic gonadotropin level (hCG) (12.02 MOM), and a down syndrome risk of 1:55. Ultrasound evaluation of the fetus indicated the presence of an atrial septal defect and clinodactyly. Cytogenetic analyses of various fetal tissues using fluorescence in situ hybridization (FISH) failed to detect substantial numbers of trisomy 16 cells; however, trisomy 16 mosaicism was identified in placental tissue. Molecular genetic analysis at five different loci [four analysed by polymerase chain reaction (PCR) and one by Southern blot analysis] failed to show any evidence for uniparental disomy. Although trisomy 16 cells could not be clearly demonstrated in the fetus, the presence of a clinically significant proportion of aneuploid cells early in development could not be excluded and it therefore cannot be assumed that a 'confined placental mosaicism' existed. The markedly elevated hCG and elevated MSAFP levels are consistent with abnormal placental function in trisomy 16 mosaicism. Serial ultrasound evaluation (to detect any late-onset growth retardation) and fetal echocardiography may be indicated for patients with extraordinarily high levels of hCG, especially if MSAFP is also elevated.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/6. A complex chromosome rearrangement with at least five breakpoints studied by fluorescence in situ hybridization.A newborn infant with multiple congenital anomalies was diagnosed with an unbalanced translocation of chromosomes 1 and 5. Studies of parental chromosomes revealed a complex rearrangement in the patient's mother involving the exchange of terminal long arms between chromosomes 1 and 5 and the insertion of an interstitial segment from the same chromosome 5q into chromosome 2q by high-resolution G-banding. Further study of the mother's chromosomes by fluorescent in situ hybridization (FISH) detected an additional insertion between the rearranged chromosomes 2 and 5, which was not revealed by G-banding. This led to the identification of a complex translocation-insertion between 3 chromosomes with at least 5 breaks [t(1;5;2)(1pter--> 1q42.3::5q23.2-->5qter;5pter-->5q21.2:: 2q33--> 2q35::1q42.3-->1qter;2pter-->2q33::5q21 .2--> 5q23.2::2q35-->2qter)] and illustrates the value of FISH as an adjunct to standard cytogenetics, particularly in cases of complex rearrangements.- - - - - - - - - - ranking = 5keywords = hybridization (Clic here for more details about this article) |
6/6. Second 46,XX male with MLS syndrome.We report on a second 46,XX male with microphthalmia with linear skin defects (MLS) syndrome. In addition to microphthalmia and linear skin streaks, he had a secundum ASD, hypospadias with chordee, anal fistula, and agenesis of corpus callosum with colpocephaly. biopsy of a linear streak showed smooth muscle hamartomata rather than the presumed dermal aplasia. Detailed ophthalmologic examination did not show retinal lacunae typical of aicardi syndrome. dna studies with distal Xp specific probes indicated a deletion in one x chromosome and fluorescence in situ hybridization (FISH) studies with X- and Y-specific probes demonstrated the presence of a derivative x chromosome from an X;Y translocation.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |