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Lakshmi Rao Kandukuri, Venkata Padmalatha,
Murthy Kanakavalli,
Raseswari Turlapati,
Mangalipally Swapna,
Metuku Vidyadhari,
Govindaraghavan Saranaya,
Kattera Himaja,
Mamata Deenadayal,
Bipin Kumar Sethi, [......],
Nalini Gupta,
Baidyanath Chakraborthy,
Pratibha Nallari,
Lalji Singh,
C.-W Baumer,
P D Cheng,
P Cotter,
A Saccucci,
G Sazci,
Vogt
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ABSTRACT: Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30–40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months) with low level of oestrogen and raised level of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH > 20 IU/l) occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22) and q28) and (mos,45XO/46,X+ringX) involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.
Journal of Cancer Therpy. 02/2012; 8.
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Lakshmi Rao Kandukuri, Venkata Padmalatha,
Murthy Kanakavalli,
Raseswari Turlapati,
Mangalipally Swapna,
Metuku Vidyadhari,
Govindaraghavan Saranaya,
Kattera Himaja,
Mamata Deenadayal,
Bipin Kumar Sethi,
Prasun Deb,
Nalini Gupta,
Baidyanath Chakraborthy,
Pratibha Nallari,
Lalji Singh
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ABSTRACT: Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30-40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months) with low level of oestrogen and raised level of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH > 20 IU/l) occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22) and q28) and (mos,45XO/46,X+ringX) involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.
Case reports in genetics. 01/2012; 2012:640563.
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Bineet Panda,
Lakshmi Rao,
Durgadatta Tosh,
Hridesh Dixit, Venkata Padmalatha,
Murthy Kanakavalli,
Turlapati Raseswari,
Mamata Deenadayal,
Nalini Gupta,
Baidyanath Chakrabarty,
Pratibha Nallari,
Lalji Singh
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ABSTRACT: Present study was designed for carrying out the mutational analysis of the entire Androgen receptor (AR) gene including two microsatellite (CAG)n, (GGN)n, promoter region in cases of premature ovarian failure (POF) and primary amenorrhea (PA).
Previous reports of AR knockout mice model showed POF phenotype, this draws an attention on the role of AR gene in the aetiology of POF for the case-control association studies in POF samples (n = 133), PA samples (n = 63) and control samples (n = 200).
We identified six mutations including four novel mutations, i.e. c.636G > A, c.1885 + 9C > A, c.1948A > G, c.1972C > A, and two previously reported mutations, i.e. c.639G > A, c.2319-78T > G. Repeat length variation was noted in the two microsatellite regions CAG and GGN, located in the coding region of exon 1 at the N-terminal region of the AR gene. The CAG repeat length was homogeneously distributed with the same frequency and no association among all cases and controls. The GGN repeat showed a significant association among the SS and SL allele with p = 0.0231 and p = 0.0476, respectively, among the POF/control samples.
Thus, AR gene mutations may play a role in the genetic cause of POF. Identification of the underlying genetic alteration of the AR gene is important for a proper diagnosis of POF subjects.
Gynecological Endocrinology 08/2011; 27(8):572-8. · 1.58 Impact Factor
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Hridesh Dixit,
Lakshmi Rao, Venkata Padmalatha,
Turlapati Raseswari,
Anil Kumar Kapu,
Bineet Panda,
Kanakavalli Murthy,
Durgadutta Tosh,
Pratibha Nallari,
Mamata Deenadayal,
Nalini Gupta,
Baidyanath Chakrabarthy,
Lalji Singh
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ABSTRACT: Premature ovarian failure (POF) is unexplained amenorrhoea (>6 months), increased FSH (>20 IU/l) and LH occurring before 40 years. Several genes are reported as having significance in POF, including genes governing regulation of the hypothalamic-pituitary-ovarian axis, but their role in ovarian physiology is not known. Deletions or translocations in Xq arm have been found to be associated with POF, assuming presence of ovarian-related genes but ovary-related function of these genes is unclear. Several researchers have suggested specific loci on Xq critical region, POF1 and POF2 and genes DIA, FMR1 and FMR2. The understanding of ovarian physiology, its regulation and genes involved is important to explain the causes of POF. Some genes coordinate development of germ cell to primordial stage, e.g. GDF9, BMP15 and NGF, while others regulate development of further stages, such as FSH and LH. Mutation in these genes may lead to female infertility and are likely to be candidate genes for POF. Recently, association between blepharophimosis-ptosis-epicanthus inversus syndrome type 1 and POF has emerged as a possibility. Galactosaemia is also shown to be important in POF due to toxic effects of accumulated galactose or downstream products. Thus, understanding the role of several genes can be used for the appropriate genetic diagnosis, research and in the clinical practice of POF.
Reproductive biomedicine online 03/2010; 20(6):724-40. · 2.04 Impact Factor
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ABSTRACT: The common cause of mental impairment and the wide range of physical abnormalities is balanced chromosome rearrangement. As such, it is difficult to interpret, posing as a diagnostic challenge in human development. We present a unique familial case report with the paternally inherited autosomal-balanced reciprocal translocation involving chromosomal regions 8q and 18q. The etiology of the translocation, i.e. 46,XX,t(8;18)(q22.1;q22) was detected by conventional high-resolution Giemsa-Trypsin-Giemsa-banding and fluorescence in situ hybridization techniques. The father was found to be the carrier of the chromosome defect and also the same was observed in the first female child referred with a history of delayed milestone development. However, the second female child showed normal 46, XX karyotype. This is the first report of reciprocal translocation involving 8q and 18q associated with the delayed milestone development. The reason likely may be due to the rearrangement of genetic material at these breakpoints having a crucial relationship and thus manifesting developmental delay in the progeny. Accordingly, this paper also shows genetic counseling discussion for the cause.
Journal of Pediatric Neurosciences 01/2010; 5(1):64-7.
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ABSTRACT: Male DNA of recognized fetal origin can be detected in the maternal circulation many years after delivery. It is referred to as fetal microchimerism, and is thus a possible explanation for the existence of low-level Y chromosome mosaicisms. Employing the nested polymerase chain reaction (PCR) technique, Y-specific markers were investigated in 13 cases with abnormal sex chromosome and 31 normal women. Sex-determining region Y (SRY) sequences were detected in normal women with a male child, which reflects the existence of fetal progenitor cells in the maternal circulation. This was completely absent in normal women with a female child. Individuals with the Y chromosome showed amplification for Y-specific markers. Microchimerism of Y was noted in Turner phenotype cytogenetically investigated with marker chromosome, and in an individual with XX karyotype. False positive amplifications are possible in nested PCR reactions, but the same could also be true for routine PCR. However, in the absence of any identifiable factor that could contribute to the recurrence of spurious PCR amplifications, cases of therapeutic importance must be tested at least five times. In such situations, DNA from an additional tissue should also be used for nested PCR.
Reproductive biomedicine online 11/2008; 17(4):575-8. · 2.04 Impact Factor
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ABSTRACT: HLA-G is a nonclassical histocompatibility complex member associated with fetal tolerance of the mother observed during pregnancy. Despite its being a less polymorphic gene, a number of studies have evaluated the role of HLA-G gene polymorphisms on the risk of pregnancy-related complications. A 14-bp deletion polymorphism in exon 8 (3'UTR) was known to influence the levels of soluble HLA-G, differential splicing of the transcript, and also the induction of interleukin-10 secretion. The present study is aimed at evaluating the variations in exon 2 and exon 8 of the HLA-G gene for the risk of recurrent miscarriages in South Indian women. A total of 169 cases and 92 controls are included in the study. Six novel polymorphisms were identified, 2 of which are in intron 2 near the exon-intron junction and 4 of which are present downstream to the 14-bp deletion in 3'UTR. The exon 2 and intron polymorphisms failed to show any association. The T1570C and C1594A polymorphisms showed a significant association (P = .002 and .021) with the risk of miscarriage after categorization based on the 14-bp deletion. Linkage disequilibrium analysis showed that the T allele of T1570C is in linkage disequilibrium with the 14-bp deletion in cases but not in controls. In silico RNA folding studies indicate that the T allele forms a more stable secondary structure than the C allele, giving rise to a more stable transcript.The authors demonstrate a significant relation between the two 3'UTR polymorphisms and recurrent miscarriages.
Reproductive sciences (Thousand Oaks, Calif.) 06/2008; 15(8):817-24. · 2.31 Impact Factor
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ABSTRACT: Studies on the relation between endothelial nitric oxide synthase (eNOS) activity in implantation and maintenance of pregnancy highlights the importance of eNOS gene polymorphisms in recurrent early pregnancy loss (REPL). We investigated the relationship between idiopathic REPL and polymorphisms in eNOS among South Indian women.
A case-control study comprising 145 females with REPL and 99 control females. The polymorphisms studied include a 27 bp intron 4 repeat, Glu298Asp variation of exon 7 and a novel 140 A --> G polymorphism in intron 6. A polymerase chain reaction-based di-deoxy dye terminator sequencing method was used for genotyping.
A novel A --> G polymorphism was identified in intron 6. The more frequent b allele of intron 4 repeat was present at a frequency of 0.84 in cases as compared to 0.86 in controls (O.R 1.17); the G allele of exon 7 coding for the wild-type glutamate containing isoform was present at a frequency of 0.79 in cases and 0.83 in controls (O.R 1.30, CI 0.6-2.8). The intron 6 variant A allele was present at a frequency of 0.58 in cases and 0.45 in controls (O.R 0.59, CI 0.33-1.08). Overall, the polymorphism in intron 6, in homozygous condition, exhibited a significant association to the risk of REPL (O.R 0.43, CI 0.21-0.89), P: 0.021).
The present study identifies and validates a novel polymorphism in the eNOS gene which was found associated with the risk of REPL.
Archives of Gynecology and Obstetrics 06/2006; 274(2):119-24. · 1.28 Impact Factor
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ABSTRACT: Abstract Premature ovarian failure (POF) may be idiopathic or may be associated with genetic or autoimmune disorders. It is well known that chromosomal defects can impair ovarian development and its function. It is estimated that X-chromosome abnormalities occur in 10-25% of women with abnormal ovarian function. Of these, the common chromosome defects reported are either true Turner's karyotype or its variants. We describe a novel X-chromosome aberration in a woman with primary amenorrhea. Cytogenetic and fluorescence in situ hybridization analysis revealed a short-arm deletion of X-chromosome as a Turner's variant [mos,45,XO/46,Xdel(X)(p11.1-p22.3)]. This interesting and rare case with unique X-chromosome defect reveals an additional mechanism for the cause of POF.
Journal of Obstetrics and Gynaecology Research 03/2005; 31(1):12-5. · 0.94 Impact Factor
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ABSTRACT: Various factors cause spermatogenesis arrest in men and, in a large number of cases, the underlying reason still remains unknown. Little attention is paid to determining the genetic defects of varicocele-related infertility. The objective of our present study was to investigate the chromosomal abnormalities and Y chromosome microdeletions in infertile men of South Indian origin with varicocele and idiopathic infertility. Metaphase chromosomes of 251 infertile men with varicocele and unexplained infertility were analyzed using Giemsa-Trypsin-Giemsa (GTG) banding and fluorescence in situ hybridization (FISH). The microdeletions in 6 genes and 18 sequence-tagged-sites (STS) in the Yq region were screened using polymerase chain reaction (PCR) techniques. Out of 251 infertile men, 57 (22.7%) men were with varicocele, of which 8.77% were azoospermic, 26.31% were severely oligozoospermic, 21.05% were mildly oligozoospermic, and 43.85% were oligoasthenoteratozoospermic (OAT), and 194 (77.29%), with idiopathic infertility, of which 51% were azoospermic, 13.40% were severely oligozoospermic, 19.07% were mildly oligozoospermic, and 16.4% were with OAT. Genetic defects were observed in 38 (15.13%) infertile individuals, including 14 (24.56%) men with varicocele and 24 (12.37%) men with idiopathic infertility. The frequencies of chromosomal defects in varicocele and idiopathic infertility were 19.3% and 8.76%, respectively, whereas Y chromosome microdeletions were 5.26% and 3.60%, respectively. Overall rate of incidence of chromosomal anomalies and microdeletions in 251 infertile men were 11.5% and 3.98%, respectively, indicating a very significant higher association of genetic defects with varicocele than idiopathic male infertility. Our data also demonstrate that, among infertile men with varicocele, severely oligozoospermic and OAT men with varicocele have higher incidences of genetic defects than mildly oligozoospermic and azoospermic men.
Journal of Andrology 25(1):147-53. · 2.97 Impact Factor
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ABSTRACT: To establish the risk associated with mutations in the coding region of GDF9 gene in Indian women with ovarian failure.
This case-control study was designed for mutational analysis of the GDF9 coding region in a cohort of women with premature ovarian failure (n = 127), primary amenorrhea (n = 58), and secondary amenorrhea (n = 10) compared with controls (n = 220).
This case-control study revealed eight mutations in the GDF9 gene, including five novel mutations: c.1-8C>T, c.199A>C (p.Lys67Glu), c. 205C>T, c.646G>A (p.Val216Mat), and c.1353C>T, and three documented mutations: c.398-39C>G, c.447C>T, and c.546G>A. Missense mutation c.199A>C was present in 4 of 127 premature ovarian failure (POF) cases and 1 of 10 secondary amenorrhea cases. The c.646G>A mutation was present in two POF cases. Both missense mutations were absent in controls. Genotype distribution of c.447C>T was significantly different in POF cases than controls (chi(2) = 5.93, P = 0.05). We chose two frequent single-nucleotide polymorphisms (c.398-39C>G, c.447C>T) for haplotyping and found that the C-T haplotype was significantly higher in patients (P = 0.03), whereas the C-C haplotype was representative of the control group.
We report two rare missense mutations, c.199A>C and c.646G>A, which are associated with ovarian failure. The presence of the c.447>T mutation might indicate a higher risk for POF. Haplotype C-T was significantly associated with ovarian failure, whereas the C-C haplotype was representative of the control group.
Menopause 12(6):749-54. · 3.76 Impact Factor
