Indian J Hum Genet
· 2012 May · PMID 23162304
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Chromosome inversions are intra-chromosomal rearrangements formed when the chromosome breaks occur at two places, and in the process of repair the intervening segments are joined in an inverted or opposite manner. Invers...Chromosome inversions are intra-chromosomal rearrangements formed when the chromosome breaks occur at two places, and in the process of repair the intervening segments are joined in an inverted or opposite manner. Inversions themselves do not appear to cause clinical anomalies, if balanced. Abnormal phenotypes can occur due to gene disruption at the point of breakage and reunion or due to duplication/deficiency recombinants formed during crossover at meiosis. We report a case with familial deletion 4q syndrome in a 1-year-old female child with dysmorphism and congenital abnormalities. The deletion was an outcome of a paracentric inversion 4q31.2q35.2. The deletion was confirmed by fluorescence in situ hybridization using telomeric DNA probes for chromosome No. 4. An attempt was made to correlate the genotype with the phenotype. The father had the same rearrangement with a milder phenotype. The recurrence risk in such cases is high.
Indian J Hum Genet
· 2012 May · PMID 23162303
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Smith-Lemli-Opitz syndrome is an autosomal recessively inherited disorder. A severe defect in cholesterol biosynthesis has been identified leading to abnormally low plasma cholesterol levels and elevated levels of the ch...Smith-Lemli-Opitz syndrome is an autosomal recessively inherited disorder. A severe defect in cholesterol biosynthesis has been identified leading to abnormally low plasma cholesterol levels and elevated levels of the cholesterol precursor 7-dehydrocholesterol, the result of deficiency of 7-dehydrocholesterol reductase. We describe one such child with Smith-Lemli-Opitz syndrome. This child had clinical features similar to Smith-Lemli-Opitz syndrome like facial dysmorphism and cardiac and renal anomalies with failure to thrive.
Indian J Hum Genet
· 2012 May · PMID 23162302
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Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt susp...Crigler-Najjar syndrome type 2 is a rare cause for persistent unconjugated hyperbilirubinemia, inherited in an autosomal recessive manner. Even though it is compatible with normal life span, in the absence of prompt suspicion and intensive management it can prove fatal not only in the neonatal period but also during adult life. Here, we describe a case with a novel homozygous UGT1A1 p.Pro176Leu mutation.
Indian J Hum Genet
· 2012 May · PMID 23162301
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Chronic myeloid leukemia (CML) is characterized by a Ph(1) chromosome that derives through a translocation between chromosomes 9 and 22, i.e., t (9;22). Identifying the Ph(1) chromosome through cytogenetic analysis is an...Chronic myeloid leukemia (CML) is characterized by a Ph(1) chromosome that derives through a translocation between chromosomes 9 and 22, i.e., t (9;22). Identifying the Ph(1) chromosome through cytogenetic analysis is an important aspect of CML diagnosis. The aim of this study was to determine the significance of cytogenetic analysis in the diagnosis of CML as well as to find out a relationship between chromosomal abnormalities and CML patients in different stages of treatment. Six CML patients were investigated for this study. The presence of Ph(1) chromosome was detected at different times of treatment using GTG banding on peripheral blood or bone marrow aspirations, and the results were analyzed using cytovision workstation. Hematological features were compared between newly diagnosed patients and patients under treatment. The Ph(1) chromosome was strongly associated with all cases of CML. The regression of Ph(1) chromosomes differed for each patient depending on the treatments and individual response to specific treatments.
Indian J Hum Genet
· 2012 May · PMID 23162300
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Ultrasound (USG) is a useful investigation in obstetrics. Its mean indications include screening for fetal anomaly, especially for Down's syndrome and other genetic trisomy. Here, the author tries to access the compatibi...Ultrasound (USG) is a useful investigation in obstetrics. Its mean indications include screening for fetal anomaly, especially for Down's syndrome and other genetic trisomy. Here, the author tries to access the compatibility between classical USG scoring index and the new likelihood ratio-based system. New recommendation on severity of studied markers is given.
Indian J Hum Genet
· 2012 May · PMID 23162299
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BACKGROUND: Dopaminergenic system plays an essential role in the plasticity of the human brain. The dopamine transporter gene (SLC6A3) mediates active reuptake of dopamine from synapsis, terminates dopamine signals, and...BACKGROUND: Dopaminergenic system plays an essential role in the plasticity of the human brain. The dopamine transporter gene (SLC6A3) mediates active reuptake of dopamine from synapsis, terminates dopamine signals, and therefore, is implicated in a number of dopamine-related disorders like psychosis. Variations in the form of single nucleotide polymorphisms in the core promoter of the SLC6A3 gene are reported to be involved in the pathogenesis of schizophrenia. In this study, we also attempted to establish the possible role of the polymorphism G-660C in the SLC6A3 gene promoter in schizophrenia in a case-control study. MATERIALS AND METHODS: The allele and genotype frequency were analyzed in an Iranian cohort of 200 unrelated patients and 200 controls using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotype frequency for case and control groups was GG 100%, GC 0%, CC 0%, and GG 100%, GC 0%, CC 0%, respectively. The C allele was failed in both groups. CONCLUSION: Our data suggest clearly that there is no association between the -660G/C polymorphism and outcome of schizophrenia in the Iranian population.
Indian J Hum Genet
· 2012 May · PMID 23162298
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Families with at least 2 or more individuals having hereditary hearing loss were enrolled from different areas of Khyber Pakhtoonkhwa, mainly from district Peshawar. Detailed history was taken from each family to minimiz...Families with at least 2 or more individuals having hereditary hearing loss were enrolled from different areas of Khyber Pakhtoonkhwa, mainly from district Peshawar. Detailed history was taken from each family to minimize the presence of other abnormalities and environmental causes for deafness. Families were questioned about skin pigmentation, hair pigmentation, and problems relating to balance, vision, night blindness, thyroid, kidneys, heart, and infectious diseases like meningitis, antibiotic usage, injury, and typhoid. The pedigree structures were based upon interviews with multiple family members, and pedigrees of the enrolled families were drawn using Cyrillic program (version 2.1). All families showed recessive mode of inheritance. I studied 8 families of these 10. For linkage analyses, studies for DFNB1 locus, 3 STR markers (D13S175, D13S292, and D13S787) were genotyped using polyacrylamide gel electrophoresis (PAGE) and haplotypes were constructed to determined, linkage with DFNB1 locus. From a total of 8 families, a single family-10 showed linkage to DFNB1 locus.
Ghosh D, Sinha S, Chatterjee A
… +1 more, Nandagopal K
Indian J Hum Genet
· 2012 May · PMID 23162297
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INTRODUCTION: Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21. AIM: Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT)(n) and...INTRODUCTION: Down syndrome (DS), the leading genetic cause of mental retardation, stems from non-disjunction of chromosome 21. AIM: Our aim was to discern non-disjunction in DS patients by genotyping GluK1-(AGAT)(n) and D21S2055-(GATA)(n) microsatellites on chromosome 21 using a family-based study design. MATERIALS AND METHODS: We have used a PCR and automated DNA sequencing followed by appropriate statistical analysis of genotype data for the present study RESULTS AND DISCUSSION: We show that a high power of discrimination and a low probability of matching indicate that both markers may be used to distinguish between two unrelated individuals. That the D21S2055-(GATA)(n) allele distribution is evenly balanced, is indicated by a high power of exclusion [PE=0.280]. The estimated values of observed heterozygosity and polymorphism information content reveal that relative to GluK1-(AGAT)(n)[H(obs)=0.286], the D21S2055- (GATA)(n)[H(obs)=0.791] marker, is more informative. Though allele frequencies for both polymorphisms do not conform to Hardy-Weinberg equilibrium proportions, we were able to discern the parental origin of non-disjunction and also garnered evidence for triallelic (1:1:1) inheritance. The estimated proportion of meiosis-I to meiosis-II errors is 2:1 in maternal and 4:1 in paternal cases for GluK1-(AGAT)(n), whereas for D21S2055-(GATA)(n), the ratio is 2:1 in both maternal and paternal cases. Results underscore a need to systematically evaluate additional chromosome 21-specific markers in the context of non-disjunction DS.
Akbari MT, Behjati F, Pourmand GR
… +2 more, Asbagh FA, Kachoui MA
Indian J Hum Genet
· 2012 May · PMID 23162296
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BACKGROUND: Infertility affects approximately 10%-15% of couples in reproductive age. In half of the couples, causes are male-related, associated with impaired spermatogenesis. There is a complex correlation between gene...BACKGROUND: Infertility affects approximately 10%-15% of couples in reproductive age. In half of the couples, causes are male-related, associated with impaired spermatogenesis. There is a complex correlation between genetics and infertility. Several factors affect on gametogenesis, from which factors that lead to chromosomal abnormalities are one of the best known. The aim of this study was to determine type and rate of chromosomal abnormalities in infertile azoospermic and oligospermic males in Iranian population. MATERIALS AND METHODS: The records of a total of 222 participants were evaluated retrospectively. RESULTS: As a whole we observed 13.96% chromosomal abnormality, from which 12.15% showed numerical and 1.8% showed structural abnormalities. CONCLUSION: Comparison of our results with the review of the literature shows a higher incidence (4- fold) of gonosomal, in particular, numerical gonosomal, chromosomal anomalies. Cytogenetic analysis is strongly suggested for infertile men, particularly in those who suffer from azoospermia.
Ansari SH, Shamsi TS, Ashraf M
… +8 more, Farzana T, Bohray M, Perveen K, Erum S, Ansari I, Ahmed MN, Ahmed M, Raza F
Indian J Hum Genet
· 2012 May · PMID 23162295
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BACKGROUND: β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseli...BACKGROUND: β -Thalassaemia, an autosomal recessive hemoglobinopathy, is one of the commonest genetically transmitted disorders throughout the world. Collective measures including carrier identification, genetic counseling and prenatal diagnosis are required for preventing β-thalassemia. AIM: To achieve this objective, Identification of the spectrum of genetic mutations, especially for various ethnic backgrounds in Pakistan. Therefore, we designed a cross sectional prospective study to identify the frequency of various gene mutations in different ethnic groups of Pakistan. MATERIALS AND METHODS: Over a 5-year period, DNA from 648 blood samples {including specimens of chorionic villus sampling (CVS)} were analyzed for the twelve most common β-thalassemia mutations found in the Pakistani population by a Multiplex amplification refractory mutation system (ARMS). Each sample was analyzed for the mutation as well as the normal gene, appropriate with negative and positive controls, and reagent blanks. RESULTS: Out of 648 samples mutations were identified in 640 (98.75%) samples by multiplex ARMS. 8 common β-thalassemia mutations were identified in 8 different ethnic groups accounting for 93.9% of the β-thalasemia alleles. CONCLUSIONS: Based on the outcome of this study a cost effective proposal is formulated for detection of β-thalassemia mutations.
Indian J Hum Genet
· 2012 May · PMID 23162294
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BACKGROUND: The impact of women's menstrual cycle on her quality of life, health, work, and community is substantial. Menstrual disturbance is linked with general ill conditions such as migraine, asthma, and endocrinopat...BACKGROUND: The impact of women's menstrual cycle on her quality of life, health, work, and community is substantial. Menstrual disturbance is linked with general ill conditions such as migraine, asthma, and endocrinopathies. The clinical significance of medical interventions to prevent these conditions becomes clear if the role of genetic or environment is clarified. AIMS: To identify the genetic and environmental contribution on menstrual characteristics. SETTING AND DESIGN: This was a cross-sectional study in 2 Asian countries. MATERIALS AND METHODS: 2 cohorts of monozygotic and dizygotic twins born between (1945-1988, n = 122) and (1951-1993, n = 71) were taken. A standard questionnaire was designed inclusive of socio- demographic characteristics of subjects as well as menstrual history (duration, interval, amount, irregularity). Subjects were interviewed by phone. STATISTICAL ANALYSIS: Quantitative variables were analyzed using Falconars' formula as well as maximum likelihood analysis. Structural modeling was then applied to twin correlations to provide estimates of the relative genetic and/or environmental factors contribution in determining the measured trait. RESULTS: Menstrual characteristics were found to be under environmental influence where the best fitting model for menstrual interval and duration was common environment. CDF plotting confirmed the results for both variables. Proband-wise concordance analysis for amount of menstruation, amenorrhea, and irregular menstruation revealed no genetic influence. The best fitting model for menstrual irregularity was CE (C73%, E27%). The same model was defined for amenorrhea (C48%, E52%). CONCLUSIONS: Environmental factors are most likely responsible to determine the menstrual flow, its integrity, and regularity. These factors need to be studied further.
Indian J Hum Genet
· 2012 May · PMID 23162293
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BACKGROUND: Primary amenorrhea is defined as the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older. Hormonal disorders are main causes of primary amenorrhea. Common h...BACKGROUND: Primary amenorrhea is defined as the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older. Hormonal disorders are main causes of primary amenorrhea. Common hormonal cause of primary amenorrhea includes pituitary dysfunction and absent ovarian function. The aim of this study was to estimate the incidence and types of chromosomal abnormalities in patients with primary amenorrhea in Egypt. MATERIALS AND METHODS: Chromosomal analysis and hormonal assay were carried out on 223 patients with primary amenorrhea that were referred from different parts of Egypt to Cytogenetic laboratory of Genetic Unit, Children Hospital Mansoura University, from July 2008 to December 2010. FISH technique was carried out in some of cases to more evaluation. RESULTS: The frequency of chromosomal abnormalities was 46 (20.63%) in primary amenorrhea patients. The chromosomal abnormalities can be classified into four main types. (1) The numerical abnormalities of the X chromosome were detected in 23 (50 %). (2) Structural abnormalities of the X chromosome were detected in 11 (23.91%). (3) Mosaicism of X chromosome was found in 10 (21.74%). (4) Male karyotype 46, XY was presented in 2 (4.35%). CONCLUSION: The present study showed that karyotype and FISH are necessary to detect the causes of primary amenorrhea. This study also revealed the incidence of chromosomal abnormalities in women with primary amenorrhea in Egypt is similar to that reported in previous literatures.
Indian J Hum Genet
· 2012 May · PMID 23162292
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CONTEXT: Tumor protein 53 (tp53) is one of the candidate gene proposed for neural tube defects, which affects central nervous system during early embryonic development, on the basis of mouse models. AIMS: The present stu...CONTEXT: Tumor protein 53 (tp53) is one of the candidate gene proposed for neural tube defects, which affects central nervous system during early embryonic development, on the basis of mouse models. AIMS: The present study is an attempt to unfold the possible role of tp53 G412C polymorphism in the incidence of neural tube defect (NTDs) in humans. SETTINGS AND DESIGN: Case-control study was carried out in government hospitals of Delhi, India. MATERIALS AND METHODS: Subjects comprised of 100 mothers of NTD children and 100 matched control mothers. Information on some environmental exposures was collected along with blood samples. After DNA extraction, the genotyping of tp53 G412C polymorphism was carried out by PCR-RFLP method. STATISTICAL ANALYSYS: Fisher Exact or Chi square test, binary logistic model, and odds ratio (95% confidence interval) calculations were used to evaluate effect of risk factors on NTDs using SPSS v17.0. RESULTS: The 'CC' genotype of tp53 G412C showed protective effect towards the development of anencephaly and/or encephalocele (OR: 0.44; 95% CI: 0.19-1.00); however, no significant difference among overall NTD cases and controls was observed (P>0.05). Further segregation of all subjects based on 2 different communities, Hindus and Muslims, the association of 'CC' genotype of the polymorphism with reduced NTD risk was observed among Hindu community (OR: 0.33; 95% CI: 0.13-0.79). CONCLUSION: The study highlights the selective advantage provided by maternal 'CC' genotype, thereby reducing risk of cephalic NTDs, probably due to the lower apoptotic activity of the protein, however, more specifically in the presence of community-specific microenvironment.
Indian J Hum Genet
· 2012 May · PMID 23162291
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CONTEXT: Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR. AIMS: Molecul...CONTEXT: Survivors of the Bhopal gas disaster still suffer from various respiratory ailments. We examined the effects of exposures among a cross-section of current residents suffering from COPD by ISSR-PCR. AIMS: Molecular screening of the gas-affected population of Bhopal with COPD for microsatellite instability due to exposure of MIC. SETTINGS AND DESIGN: The isocyanate-exposed population of Bhopal city suffering from chronic obstructive pulmonary disorder. MATERIALS AND METHODS: Inter-(SSR) analysis was used to characterize microsatellite instability in 52 MIC victims of Bhopal, suffering from COPD using (CA)(8)RG and (CA)(8)R[Y-Q] primer. STATISTICAL ANALYSIS USED: Association analyses were performed using regression analysis. RESULTS: The study on the MIC-affected population in Bhopal showed weak association between microsatellite instability and age (r = + 0.37); exposure distance from site (r = -0.44); and smoking status(r = + 0.12); while regression analysis of the above parameters displayed supporting evidence. CONCLUSIONS: The high prevalence of smoking coupled with aging and poor living habits threatens, to further increase COPD incidences among this population, highlighting the need for enhanced screening efforts.
Bhukhanvala DS, Sorathiya SM, Shah AP
… +2 more, Patel AG, Gupte SC
Indian J Hum Genet
· 2012 May · PMID 23162290
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BACKGROUND: From the data of transfusion-dependent thalassemia major cases, the 4 communities (Muslim, Dhodia Patel, Kachhiya Patel, and Modh Bania) with high prevalence but not studied methodically were selected. AIM: T...BACKGROUND: From the data of transfusion-dependent thalassemia major cases, the 4 communities (Muslim, Dhodia Patel, Kachhiya Patel, and Modh Bania) with high prevalence but not studied methodically were selected. AIM: The aim of this study is to find prevalence of β-thalassemia and sickle cell anemia in 4 selected communities and also to evaluate hematological profile in them. MATERIALS AND METHODS: For screening of β-thalassemia trait (BTT) and sickle cell trait (SCT), all samples were tested for red cell indices, solubility, HbA(2) level and doubtful cases confirmed on HPLC. STATISTICAL ANALYSIS: Mean ± SD, χ(2) and 't' tests were used to evaluate the significance. RESULTS AND CONCLUSION: Among 4 selected communities, the highest prevalence of BTT was observed in Modh Bania (6.2%) and Kachhiya Patel (6.05%) and that of SCT in Dhodia Patel (14.0%). Significantly higher prevalence of BTT was observed in Memon (P < 0.0001) and of SCT in Khalifa 6.6% (P < 0.0001) compared to other Muslim sub castes. Anemia was more prevalent in BTT compared to non-BTT and non-SCT subjects. 80% of Dhodia Patel non-BTT and non-SCT subjects showed microcytic red cell morphology. Their Mean ± SD Hb concentration was 12.1 ± 1.73, hence iron deficiency cannot be a sole reason. This community needs α-thalassemia and iron studies.
Indian J Hum Genet
· 2012 May · PMID 23162289
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BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder, characterized by postnatal growth deficiency, typical dysmorphic features, broad thumbs and toes, and mental retardation. Ver...BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder, characterized by postnatal growth deficiency, typical dysmorphic features, broad thumbs and toes, and mental retardation. Very few cases are reported in literature from developing countries. Diagnosis is often delayed due to non-familiarity with the characteristic features of this syndrome. AIMS: To report 11 cases of RSTS and to review the current literature. SETTINGS AND DESIGN: Retrospective study conducted in genetic and metabolic unit of a tertiary care teaching hospital in north India over a period of 3½ years. MATERIALS AND METHODS: 11 patients with diagnosis of RSTS were identified, and their case sheets were reviewed. RESULTS: Developmental delay was presenting complaint in 10 patients, and seizure in 1 case. 7 patients had microcephaly (head circumference below -3 SD), and a prominent beaked nose was seen in 9 patients. The intelligence quotient (IQ) varied from 22-62 in 7 patients who had mental retardation. The most notable features in hands were broadness, shortening, and flattening of the distal phalanx of thumbs or great toes. Additionally, we also noted webbing of neck, microphthalmia, and pachygyria (on MRI brain) in 1 patient each. CONCLUSIONS: The diagnosis of RSTS is primarily clinical and based on characteristic phenotype that is often combined with a variety of somatic anomalies. An early diagnosis facilitates appropriate genetic counseling and in planning the management.
Indian J Hum Genet
· 2012 May · PMID 23162288
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The Toll-like receptor (TLR) family plays a fundamental role in host innate immunity by mounting a rapid and potent inflammatory response to pathogen infection. TLRs recognize distinct microbial components and activate i...The Toll-like receptor (TLR) family plays a fundamental role in host innate immunity by mounting a rapid and potent inflammatory response to pathogen infection. TLRs recognize distinct microbial components and activate intracellular signaling pathways that induce expression of host inflammatory genes. Several studies have indicated that TLRs are implicated in many inflammatory and immune disorders. Extensive research in the past decade to understand TLR-mediated mechanisms of innate immunity has enabled pharmaceutical companies to begin to develop novel therapeutics for the purpose of controlling an inflammatory disease. The roles of TLRs in the development of autoimmune diseases have been studied. TLR7 and TLR9 have key roles in production of autoantibodies and/or in development of systemic autoimmune disease. It remains to be determined their role in apoptosis, in the pathogenesis of RNA containing immune complexes, differential expression of TLRs by T regulatory cells.
Indian J Hum Genet
· 2012 May · PMID 23162287
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In recent years, the field of dentistry has embossed its presence by taking major leaps in research and further bringing it into practice. The most valuable ongoing research in regenerative dentistry is the study on stem...In recent years, the field of dentistry has embossed its presence by taking major leaps in research and further bringing it into practice. The most valuable ongoing research in regenerative dentistry is the study on stem cells. It was instituted that stem cells grow rapidly and have the potential to form specialized dentin, bone, and neuronal cells. These neuronal cells can be used for dental therapies and can provide better treatment options for patients. The stem cells based therapies could help in new advances in treating damaged teeth, inducing bone regeneration and treating neural injury as well.