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ABSTRACT: Trichohepatoenteric syndrome (THES) is characterized by chronic diarrhea, dysmorphic facies and hair abnormalities. Hepatic involvement varies from no abnormality to cirrhosis and hemochromatosis. Recently, mutations in the tetratricopeptide repeat domain 37 (TTC37) gene were identified to cause THES. The c.2808G>A variation was suggested as a possible founder mutation among the South Asians. We further report 2 unrelated cases of Asian-Indian ethnicity (Gujrati) with THES, wherein targeted mutation analysis revealed the same mutation in homozygous form in both cases. These findings, as well as haplotype analysis, corroborate the founder mutation hypothesis amongst Asian Indo-Pakistani ethnic groups. A restriction enzyme-based method is also described to identify this founder mutation. One of our probands had multiple hepatic hemangiomas, a feature not previously observed in this syndrome.
Molecular syndromology 08/2012; 3(2):89-93.
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ABSTRACT: Gaucher disease in India has been reported only in a few case reports from India. The aim of the study was to assess the response to enzyme replacement therapy in Indian patients with Gaucher disease.
Retrospective analysis of patients receiving CHO-derived recombinant macrophage-targetted glucocorebrosidase.
Five centers from India with experience in treating lysosomal storage disorders.
The diagnosis of Gaucher disease was confirmed by low glucocerebrosidase levels, though it was first made on splenectomy in 8 and on bone marrow examination in 9 patients. Twenty five of 52 patients diagnosed with Gaucher disease (17 Type I, 8 mild Type III) received treatment for >6 months. Indications for treatment included symptomatic anemia, thrombo-cytopenia, organomegaly, bone disease or mild neurological symptoms leading to impairment of quality of life. Patients with significant neurological involvement were excluded. The drug infusions were given intravenously every 15 days.
Hemoglobin, platelet counts, liver and spleen volumes and growth parameters.
22 of the 25 children who survived were analyzed. After 6 months of treatment, the mean (range) increase in hemoglobin was 1.5 (-3.4 to 6.1) g/dL (P=0.01) and in platelet count was 32 x 10(9)/L (-98.5 x 109 to 145.5 x10(9))/L (P=0.02). The mean (range) increase in weight was 3 kg (-5.6 to 10.5) (P=0.04) and in height was 7.1 cm (0 to 26.5) (P=0.0003). Liver size decreased by a mean (range) of 38.5% (- 5.5 to 86.7) (P=0.0003) and the spleen size by 34.8% (0 to 91.7) (P=0.004). All patients had improvement in bone pains and in 2 patients, neurological symptoms improved with others remaining static.
This is the first reported cohort of patients in India reporting our experience with imiglucerase enzyme replacement therapy for treatment of Gaucher Disease in India.
Indian pediatrics 10/2011; 48(10):779-84. · 1.05 Impact Factor
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S R Phadke,
N Gupta,
K M Girisha,
M Kabra,
M Maeda,
E Vidal,
A Moser,
S Steinberg,
R D Puri, I C Verma,
N Braverman
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ABSTRACT: Rhizomelic chondrodysplasia punctata is a rare autosomal recessive disorder characterized by stippled epiphyses and rhizomelic shortening of the long bones. We report 3 subjects of rhizomelic chondrodysplasia punctata from India and the PEX7 mutations identified in them. The common PEX7-L292X allele, whose high frequency is due to a founder effect in the northern European Caucasian population, was not identified in these patients. Instead, 2 novel alleles are described, including 64_65delGC, which was present on a single PEX7 haplotype and could represent a common allele in the Indian population.
Journal of applied genetics 01/2010; 51(1):107-10. · 1.66 Impact Factor
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ABSTRACT: Congenital adrenal hyperplasia (CAH) is the commonest cause of female pseudohermaphroditism. It is most often due to steroid 21-hydroxylase deficiency resulting from mutations in the CYP21 gene. This study was conducted to characterize mutations in the CYP21 gene, determine their frequency and correlate genotype with phenotype in Indian children with CAH. Twenty-eight patients with salt-wasting (SW) or simple-virilizing (SV) forms of the disease as well as parents and siblings were studied. Allele specific PCR was carried out and rapid characterization of six mutations was achieved in 23 patients. Twelve patients were homozygous for the mutations and 11 were heterozygous, of whom eight were compound heterozygotes and three were hemizygotes; no mutation was found in five patients. The homozygosity of the mutations was found to be high in our population. The most common mutation was Ile173Asn (31.8%), followed by intron2 splice (27.2%), Gln319stop (22.7%), gene deletion (15.9%) and Pro31Leu (2.2%). Genotype-phenotype correlations showed that the most frequent mutations in the SW group were intron2 splice and Gln319stop mutations (33.3% each) and Ile173Asn (71.4%) in the SV group.
Journal of pediatric endocrinology & metabolism: JPEM 02/2001; 14(1):27-35. · 0.88 Impact Factor
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ABSTRACT: Little is known about the heterozygous frequency of factor VIII gene markers in the Asian Indian population. The objective of this study was to establish the heterozygous frequency of polymorphic markers within and flanking the factor VIII gene in Indians and identify those most informative for carrier screening and prenatal diagnosis. Factor VIII gene polymorphism analysis at intragenic and extragenic sites was carried out by the polymerase chain reaction (PCR) method and Southern blot procedure. Sixty-three Asian Indian haemophiliacs and their families were screened. A control group of 150 women from nonhaemophilic families were screened for two markers, HindIII and BclI. Among the intragenic markers studied, the HindIII restriction fragment length polymorphism (RFLP) showed the highest heterozygous frequency (0.52) followed by the intron 13 (0.47) and intron 22 (0. 44) short tandem repeats (STRs). Among extragenic markers, TaqI had the highest heterozygous frequency (0.75) followed by BglII (0.54). The intron 22 inversion mutation was observed in eight (40%) of 20 severe cases. In the population studied the most diagnostic polymorphisms were the intragenic markers, intron 22 (70%) STR followed by the intron 13 (52%) STR and HindIII (52%) RFLP, and the TaqI (50%) extragenic marker. Application of HindIII, BclI and the intron 22 dinucleotide repeat combined were diagnostic in 87.2% of haemophilia A families studied.
Haemophilia 12/2000; 6(6):625-30. · 2.60 Impact Factor
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American Journal of Medical Genetics 08/2000; 93(2):161-3.
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ABSTRACT: Cytogenetics investigations, mostly from peripheral blood, were carried out in 30 children with CML. Amongst a sample of 30 patients, 18 had chronic myeloid leukemia of adult variety (ACML), while the remaining 12 children had the juvenile type of chronic myeloid leukemia (JCML). Sixteen (88.9%) out of the 18 patients suffering from ACML tested positive for the classical Philadelphia chromosome translocation t(9; 22). Of the remaining two ACML patients, one tested positive for t(9; 13; 22) while no visible chromosomal changes were observed in the other patient. The activity of Nucleolar Organizer Region (NOR) was significantly reduced in 11 (61.1%) of the 18 patients suffering from ACML, when compared to that of 21 normal healthy controls. Ten out of the 12 patients suffering from JCML had normal karyotypes, while monosomy 8 and 21 q deletion were seen in the remaining two patients respectively. Amongst the 30 CML patients, chromosomal abnormalities were observed in 19 patients. Variant Philadelphia chromosome translocation (9; 13; 22) and monosomy B were observed in ACML and JCML, respectively. In two ACML patients, cytogenetic studies were helpful in diagnosis of the disease.
The Indian Journal of Pediatrics 03/2000; 67(2):107-12. · 0.52 Impact Factor
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Indian pediatrics 10/1999; 36(9):917-20. · 1.05 Impact Factor
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ABSTRACT: The usefulness of the clinical score based on Turner 5-trait scale prior to undertaking cytogenetic or molecular tests for the diagnosis of the fragile X(A) syndrome was evaluated. Mean clinical score in fragile X positive patients was significantly higher than in fragile X negative patients (7.06 +/- 1.85 vs 2.98 +/- 1.6, P < 0.0001). Of 1206 children with mental retardation 360 (29.8%) boys fulfilled defined clinical criteria to be screened for fragile X syndrome by chromosomal studies. Twenty three (6.38%) of them were found to be positive for fragile X syndrome using cytogenetic techniques. Molecular confirmation in 21 affected boys (two were lost to follow up) showed full mutation in 19 (5.27%). Two patients showed a normal 5.2 kb band on southern blot. This frequency (5.27%) of fragile X(A) patients among children with non-specific mental retardation is comparable to the results of studies in the West. Routine use of the clinical score, and the selection of patients with a score > or = 5 for diagnostic tests would reduce the laboratory load, especially in countries with limited facilities.
The Indian journal of medical research 08/1998; 108:12-6. · 1.84 Impact Factor
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Cancer Genetics and Cytogenetics 05/1998; 102(2):151-2. · 1.39 Impact Factor
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ABSTRACT: The utility of polymerase chain reaction (PCR) amplification of amelogenin gene as a reliable and rapid means of determination of sex chromosomes was tested in 20 patients of X-linked disorders (Duchenne muscular dystrophy, haemophilia and Wiscott-Aldrich and Hunter's syndromes), 12 of intersex (testicular feminization syndrome, male pseudohermaphrodites, true hermaphrodites) and 21 of congenital adrenal hyperplasia. Of these, 26 (49%) cases were for prenatal diagnosis of X-linked diseases and congenital adrenal hyperplasia (CAH). The presence of X and Y chromosomes was determined within 24 h of receiving the samples. The results were in conformity with cytogenetic studies in all instances. The analysis of amelogenin gene proved helpful in the diagnosis and management of these patients.
The Indian journal of medical research 05/1998; 107:182-6. · 1.84 Impact Factor
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ABSTRACT: We present our experience with the amplification refractory mutation system (ARMS) for the prenatal diagnosis of beta-thalassaemia in 415 pregnancies of 360 women. Five mutations of the beta-thalassaemia gene common in Asian Indians accounted for 89.2 per cent and rare mutations for 7.2 per cent of all mutant chromosomes, while 3.3 per cent of chromosomes remained uncharacterized. Identical mutations were present in both parents in 43.2 per cent of cases, due to caste-based marriages in India. A confirmed diagnosis was given in 401 (98.3 per cent) cases, of which a complete diagnosis (whether the fetus was normal, a carrier, or homozygous) was possible in 391 (94.2 per cent) of the cases. In 15 couples, the mutation was identified in only one parent. In nine of these, the identified mutation was not present in the fetus, predicting normal/carrier status, while in five the identified mutation was present in the fetus, suggesting carrier/affected status. The abortion rate was 3.9 per cent. Pitfalls in diagnosis were failure of oligonucleotides to work, maternal contamination, and false paternity. The ARMS provides an inexpensive, robust and non-isotopic method for the prenatal diagnosis of beta-thalassaemia in India. Recommendations are outlined for establishing a prenatal diagnostic service in developing countries.
Prenatal Diagnosis 02/1998; 18(1):1-7. · 2.11 Impact Factor
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ABSTRACT: We report the diagnosis of the newly identified mutation codon 47/48 insertion ATCT using allele specific primers by the PCR-based amplification refractory mutation system (ARMS). Using this method prenatal diagnosis was provided to five couples at risk for this mutation. The assay provides an easy, non-isotopic method for identifying this mutation in cases which remain uncharacterized after screening for the 5 'common' and 12 'rare' Indian mutations. It will be useful for screening and prenatal diagnosis in at risk couples and help in the thalassaemia control programme in India.
The Indian journal of medical research 07/1997; 105:275-7. · 1.84 Impact Factor
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ABSTRACT: We have characterized the mutations in 1050 carriers of the beta-thalassemia gene and analyzed their regional distribution in India. The majority of beta-thalassemia carriers were migrants from Pakistan and their pattern of mutations differed from the rest. The frequency of the 619-bp deletion was 33.3% among the migrants from Pakistan, 8-17% in the northern states, and less than 5% in the other states. Among non-migrant subjects, the predominant mutation was IVS-I-5 (G-->C), varying from 85% in the southern states and 66-70% in the eastern states to 47-60% in the northern states. The mutation IVS-I-1 (G-->T) was observed at high frequency among the migrants from Pakistan (26.2%), but with very low/zero frequency in the other states. Mutations at codons 8/9 (+G) and codons 41/42 (-CTTT) were distributed in all regions of India with a frequency varying from 3% to 15%. Only eight of 12 published rare mutations were observed in subjects from different parts of India. Mutations of codon 5 (-CT) and codons 47/48 (+ATCT) were found exclusively in migrants from Pakistan, and mutation -88 (C-->T) was detected only in subjects from Punjab, Haryana, and Uttar Pradesh. Using the amplification refractory mutation system technique, mutations were successfully identified in 98.2% of subjects. Overall, 91.8% of the subjects had one of the five commonest mutations [IVS-I-5 (G-->C), 34.1%; 619-bp deletion, 21.0%; IVS-I-1 (G-->T) 15.8%; codons 8/9 (+G), 12.1%, and codons 41/42 (-CTTT), 8.7%], 5.9% of the subjects had a less common mutation, while 1.8% of the carriers remained uncharacterized. The application of this knowledge has helped to successfully establish a program of genetic counselling and prenatal diagnosis of beta-thalassemia in order to reduce the burden of this disease in India.
Human Genetics 07/1997; 100(1):109-13. · 5.07 Impact Factor
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ABSTRACT: We have characterized the mutations in 1050 carriers of the β-thalassemia gene and analyzed their regional distribution in
India. The majority of β-thalassemia carriers were migrants from Pakistan and their pattern of mutations differed from the
rest. The frequency of the 619-bp deletion was 33.3% among the migrants from Pakistan, 8–17% in the northern states, and less
than 5% in the other states. Among non-migrant subjects, the predominant mutation was IVS-I-5 (G→C), varying from 85% in the
southern states and 66–70% in the eastern states to 47–60% in the northern states. The mutation IVS-I-1 (G→T) was observed
at high frequency among the migrants from Pakistan (26.2%), but with very low/ zero frequency in the other states. Mutations
at codons 8/9 (+G) and codons 41/42 (–CTTT) were distributed in all regions of India with a frequency varying from 3% to 15%.
Only eight of 12 published rare mutations were observed in subjects from different parts of India. Mutations of codon 5 (–CT)
and codons 47/48 (+ATCT) were found exclusively in migrants from Pakistan, and mutation –88 (C→T) was detected only in subjects
from Punjab, Haryana, and Uttar Pradesh. Using the amplification refractory mutation system technique, mutations were successfully
identified in 98.2% of subjects. Overall, 91.8% of the subjects had one of the five commonest mutations [IVS-I-5 (G→C), 34.1%;
619-bp deletion, 21.0%; IVS-I-1 (G→T) 15.8%; codons 8/9 (+G), 12.1%, and codons 41/42 (–CTTT), 8.7%], 5.9% of the subjects
had a less common mutation, while 1.8% of the carriers remained uncharacterized. The application of this knowledge has helped
to successfully establish a program of genetic counselling and prenatal diagnosis of β-thalassemia in order to reduce the
burden of this disease in India.
Human Genetics 05/1997; 100(1):109-113. · 5.07 Impact Factor
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ABSTRACT: A study of 2570 tribals comprising 973 from Kerala, 696 from Madhya Pradesh and 901 from Orissa revealed the frequency of sickle cell gene to vary from 0.05 to 0.31 among different communities. High frequency of the gene (0.145 or more) was observed among Chettys, Kurmars and Kondhs, who also had a substantial number of homozygous sicklers. None of those with sickle cell disease (HbSS) were more than 39 yr in age as compared with 9.9-35.3 per cent among heterozygotes (HbAS). Mean foetal haemoglobin in those with sickle cell disease varied between 9.7 to 13.5 per cent, although ti showed a slight positive correlation with total haemoglobin only among the Kondhs. Painful crises were universally observed among all tribals with sickle cell disease, with jaundice being present in 57.5 per cent of cases. Some carriers of sickle cell gene also complained of painful crises. A health plan for identifying homozygotes in infancy with appropriate medical management is highly desirable.
The Indian journal of medical research 04/1997; 105:111-6. · 1.84 Impact Factor
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ABSTRACT: We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene.
American Journal of Medical Genetics 02/1997; 68(2):152-7.
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ABSTRACT: A preliminary report of 13 Indian children with cystic fibrosis who were screened for the commonest mutation (delta F 508) is presented. Six (46%) patients were homozygous for delta F 508, while two patients were compound heterozygotes. Thus 14 (53.8%) of 26 mutant chromosomes had delta F 508 mutation. These findings confirm that cystic fibrosis occurs in India and all children with persistent respiratory problems and/or malabsorption should be screened for this disease.
The Indian journal of medical research 01/1997; 104:355-8. · 1.84 Impact Factor
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Indian pediatrics 12/1996; 33(11):956-60. · 1.05 Impact Factor
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ABSTRACT: Fetal blood obtained by cordocentesis was cultured to obtain rapid karyotypes of fetuses at risk during the late second trimester. Ninety nine fetal blood samples were studied for chromosomal abnormalities. The commonest indications for the procedure were abnormalities detected on ultrasonography (47.7%), and previous child with Down syndrome. Analysis of the 67 successful cultures showed four (5.9%) karyotypic abnormalities. The technique proved helpful in the obstetrical management of at risk fetuses.
The Indian journal of medical research 12/1996; 104:288-91. · 1.84 Impact Factor
