Retinoblastoma is caused by compound heterozygosity or homozygosity of retinoblastoma gene (RB1) mutations. In germline retinoblastoma, mutations in the RB1 gene predispose individuals to increased ...cancer risks during development. These mutations segregate as autosomal dominant traits with high penetrance (90%).
We screened 30 family members from one family using high resolution melting assay and DNA direct sequencing for mutations in the RB1 gene. We evaluate the phenotype and penetrance of germline mutations of the RB1 gene in a large Taiwanese family.
The molecular analysis and clinical details of this family showed phenotypic variability associated with the p.V654L mutation in exon 19 of the RB1 gene in 11 family members. The phenotype varied from asymptomatic to presence of a unilateral tumor. Only four individuals (2 males and 2 females) developed unilateral retinoblastoma, which resulted in calculated low penetrance of 36% (4/11). The four individuals with retinoblastoma were diagnosed before the age of three years. None of their relatives exhibited variable severity or bilateral retinoblastoma.
The diseased-eye ratio for this family was 0.36, which is lower than current estimates. This suggests that the RB1 p.V654L mutation is a typical mutation associated with low penetrance.
Abstract Objective We present prenatal diagnosis and molecular cytogenetic characterization of a recombinant chromosome 10 in a fetus associated with a paternal pericentric inversion. Case Report A ...35-year-old woman underwent amniocentesis at 18 weeks of gestation because of an advanced maternal age. Amniocentesis revealed a karyotype of 46,XY,der(10)del(10) (q26.3)dup(10)(p11.2p15). She underwent repeat amniocentesis at 21 weeks of gestation and array comparative genomic hybridization revealed a 31.65-Mb duplication of chromosome 10p15.3-p11.22 and a 3.07-Mb deletion of chromosome 10q26.3. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling and cytogenetic analysis revealed a karyotype of 46,XY,inv(10)(p11.2q26.3) in the father and a karyotype of 46,XX in the mother. The pregnancy was subsequently terminated, and a fetus was delivered with prominent facial dysmorphism. Postnatal cytogenetic analysis of the placenta revealed a karyotype of 46,XY, rec(10)dup(10p)inv(10)(p11.2q26.3). Fluorescence in situ hybridization analysis revealed a duplication of terminal 10p and a deletion of terminal 10q in the recombinant chromosome 10. Array comparative genomic hybridization analysis of the cord blood and umbilical cord confirmed the prenatal diagnosis. Conclusion Prenatal diagnosis of a recombinant chromosome because of an advanced maternal age should alert the possibility of a paternal pericentric inversion.
Abstract Objective This study is aimed at prenatal diagnosis of mosaic trisomy 12 and reviewing the literature. Materials and Methods A 34-year-old woman underwent amniocentesis at 17 weeks of ...gestation because of advanced maternal age. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+129/46,XX14. She was referred to the hospital for genetic counseling. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization (aCGH), interphase fluorescence in situ hybridization (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) were applied on uncultured amniocytes, and conventional cytogenetic analysis was applied on cultured amniocytes. Results The aCGH analysis on uncultured amniocytes revealed a small genomic gain in chromosome 12. Interphase FISH analysis on uncultured amniocytes using a 12q11-q12-specific probe of RP11-496H24 (green spectrum) showed three green signals in 17.8% (8/45 cells) of uncultured amniocytes. QF-PCR analysis on uncultured amniocytes using chromosome 12-specific microsatellite markers excluded uniparental disomy 12. Cytogenetic analysis of cultured amniocytes revealed a karyotype of 47,XX,+125/46,XX25. The parents decided to continue the pregnancy. A healthy 3270 g female baby was delivered at 39 weeks of gestation, with no phenotypic abnormalities. Cytogenetic analysis of the cord blood revealed a karyotype of 46,XX in 40/40 cultured lymphocytes. The neonate was normal in growth and psychomotor development at 6 months of age. Interphase FISH analysis on uncultured urinary cells revealed 5% (1/20 cells) mosaicism for trisomy 12. Conclusion Prenatal diagnosis of mosaic trisomy 12 at amniocentesis should alert a clinically significant aneuploidy. Interphase FISH and aCGH on uncultured amniocytes are useful for rapid confirmation of low-level trisomy 12 mosaicism at repeated amniocentesis.
Abstract Objective To present prenatal diagnosis of mosaic trisomy 8 and to review the literature. Materials, Methods, and Results A 34-year-old woman underwent amniocentesis at 16 weeks of gestation ...because of advanced maternal age. Amniocentesis revealed a karyotype of 47,XY,+86/46,XY31. Repeated amniocentesis at 21 weeks of gestation revealed a karyotype of 47,XY,+84/46,XY77. Interphase fluorescence in situ hybridization analysis of uncultured amniocytes showed 25% (5/20) mosaicism for trisomy 8. Array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction (QF-PCR) analyses of uncultured amniocytes revealed no genomic imbalance in chromosome 8. The result of QF-PCR excluded uniparental disomy 8. At 23 weeks of gestation, the woman underwent amniocentesis and cordocentesis at other hospitals. Amniocentesis revealed a karyotype of 47,XY,+86/46,XY10. Cordocentesis revealed a karyotype of 47,XY,+81/46,XY29. Level II ultrasound findings were unremarkable. The parents decided to continue the pregnancy. A 1373-g male baby was prematurely delivered at 29 weeks of gestation. The peripheral blood had a karyotype of 47,XY,+81/46,XY29. The infant had normal growth and mental development at 4 months of age. Conclusion Fetuses with mosaic trisomy 8 are compatible with viability and can have a favorable outcome. QF-PCR and array comparative genomic hybridization have the limitation of detection of low-level mosaicism. We suggest that in instances of repeated amniocentesis for confirmation of mosaic trisomy 8, follow-up investigations should include interphase fluorescence in situ hybridization studies on uncultured amniocytes, uniparental disomy tests, and detailed ultrasound examinations.
Objective To determine if specific mutations were present in Asian patients with progressive familial intrahepatic cholestasis (PFIC) type 2 caused by defects in bile salt export pump (BSEP), encoded ...by ABCB11. Study design A combination of denaturing high-performance liquid chromatography (DHPLC) and direct sequencing was used to screen ABCB11 mutations in 18 Taiwanese patients with low γ-glutamyltransferase PFIC or benign recurrent intrahepatic cholestasis (BRIC). Polymorphisms were also analyzed in patients with PFIC (n = 21), neonatal cholestasis (n = 23), and control subjects (n = 88). Results Seven mutations in 4 of 16 patients with PFIC from different families were detected by DHPLC, including M183V, V284L, R303K, R487H, W493X, G1004D, and 1145delC. G1004D was found in a patient with BRIC. L827I was found in another patient with neonatal cholestasis. Absent or defective BSEP staining was found in the liver of patients with mutations. Polymorphisms V444A and A865V, with an allele frequencies 75.6% and 0.6%, respectively, were found in our population. No differences were found between patients with cholestasis and control subjects. Conclusions One-fourth of Taiwanese patients with PFIC/BRIC had compound heterozygous or single heterozygous ABCB11 mutations without hot spots. All of the mutations were different from those detected in Western countries.
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder affecting myelination of the central nervous system, and is caused by mutations of the proteolipid protein 1 ( PLP1 ) gene. ...Clinical manifestations of PMD are variable and major features include progressive nystagmus, spasticity, tremor, ataxia, and psychomotor delay. We describe a classical PMD patient who had been misdiagnosed as cerebral palsy. He had nystagmus and psychomotor delay since infancy and tremor with ataxia developing gradually. Brain MRI revealed demyelination over white matter of the cerebral hemispheres and posterior limbs of the internal capsules. Positive family history led to subsequent mutation analysis, which identified a novel mutation (c.88G>C) in PLP1 in the proband, as well as his affected brother and maternal uncle, and asymptomatic maternal grandmother, mother and two sisters. Therefore, PMD should be considered in a cerebral palsy-like patient with or without positive family history. Mutation analysis is crucial for early diagnosis and further genetic counseling.
Aim: The living style, health‐care system and socio‐economic environments have changed substantially in Taiwan over past 20 years. This study was aimed to estimate the current perinatal ...cytomegalovirus (CMV) seroprevalence in northern Taiwan.
Methods: In a Taiwan Birth Panel Study, 483 pairs of mothers and neonates were prospectively recruited from one tertiary medical center, one local hospital, and two obstetric clinics located in northern Taiwan from April 2004 through January 2005. Sera of their paired maternal and cord blood were tested by an enzyme‐linked immunosorbent assay method for CMV IgG and IgM antibodies. Additional data were collected for health measures and epidemiological characteristics through trained interviewers utilising structured questionnaires.
Results: Among 483 mothers studied, 93% were Taiwanese, 6.4% were immigrants from the south‐eastern Asia and Mainland China, and 0.6% was aborigines. The seropositive rate of CMV IgG and IgM among the mothers was 91.1% and 3.5%, respectively. The immigrant mothers and the mothers younger than 20 years of age had a higher IgM seroprevalence (P < 0.05). Furthermore, 90.8% of the offspring had CMV IgG seropositivity and yet none of the neonates were CMV IgM positive.
Conclusion: The seroprevalence of CMV among childbearing women is high in northern Taiwan. The immigrant mothers and the teenage mothers appear to have higher seropositivity of CMV IgM.
The c-myc proto-oncogene encodes a ubiquitous transcription factor involved in the control of cell growth and implicated in inducing tumorigenesis. Understanding the function of c-Myc and its role in ...cancer depends upon the identification of c-Myc target genes. Nijmegen breakage syndrome (NBS) is a chromosomal-instability syndrome associated with cancer predisposition, radiosensitivity, and chromosomal instability. The NBS gene product, NBS1 (p95 or nibrin), is a part of the hMre11 complex, a central player associated with double-strand break (DSB) repair. NBS1 contains domains characteristic for proteins involved in DNA repair, recombination, and replication. Here we show that c-Myc directly activates NBS1. c-Myc-mediated induction of NBS1 gene transcription occurs in different tissues, is independent of cell proliferation, and is mediated by a c-Myc binding site in the intron 1 region of NBS1 gene. Overexpression of NBS1 in Rat1a cells increased cell proliferation. These results indicate that NBS1 is a direct transcriptional target of c-Myc and links the function of c-Myc to the regulation of DNA DSB repair pathway operating during DNA replication.
Prenatal diagnosis of mosaic tetrasomy 18p Chen, Chih-Ping; Ko, Tsang-Ming; Su, Yi-Ning ...
Taiwanese journal of obstetrics & gynecology,
12/2012, Letnik:
51, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract Objective To present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome derived from isochromosome 18p, by interphase fluorescence in ...situ hybridization (FISH) on uncultured amniocytes. Case Report A 41-year-old woman underwent amniocentesis at 18 weeks of gestation, because of advanced maternal age. Amniocentesis revealed a de novo supernumerary isochromosome 18p in two of 14 colonies of cultured amniocytes. Repeated amniocentesis was performed at 22 weeks of gestation. Interphase FISH analysis on uncultured amniocytes showed four 18p11.32-specific probe (RP11-324G2) signals in 5.7% (3/53 cells) of uncultured amniocytes. A multiplex ligation-dependent probe amplification P095 test kit and array comparative genomic hybridization analysis did not detect genomic imbalance in chromosome 18. Cytogenetic analysis of cultured amniocytes at repeated amniocentesis revealed a karyotype of 47,XY,+i(18)(p10)3/46,XY23. The pregnancy was carried to 38 weeks of gestation, and a healthy 3120 g male baby was delivered. When examined at 2 months of age, the infant was normal in growth and development, without phenotypic abnormalities. The cord blood had a karyotype of 46,XY. Polymorphic DNA marker analysis excluded uniparental disomy 18. Interphase FISH analysis on uncultured urinary cells showed 9.4% (3/32 cells) mosaicism for tetrasomy 18p. Conclusion There is cytogenetic discrepancy between amniocytes and cord blood lymphocytes in prenatally detected mosaic tetrasomy 18p. Interphase FISH on uncultured amniocytes has the advantage of rapid confirmation of low-level mosaicism for tetrasomy 18p at amniocentesis.
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