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A Pandya

Publications and source records attributed to A Pandya.

71 records · Page 4Linked to original sources
PubMed1996

Linkage studies in a large kindred with hereditary pancreatitis confirms mapping of the gene to a 16-cM region on 7q.

We report localization of the gene for autosomal dominant hereditary pancreatitis (HP) to a small region of the long arm of chromosome 7 in a large four-generation kindred. Affected family members may first become symptomatic in childhood or even infancy with progression to pancreatic calcification, pseudocyst formation, endocrine and exocrine insufficiency, and even pancreatic cancer in some cases. However, obligate gene carriers may remain virtually symptom free throughout life. HP is the most common cause of childhood pancreatitis in the United States. Gene mapping with microsatellite markers demonstrates that HP is tightly linked to the marker D7S684 (Zmax = 7.0, theta = 0.0). Three obligate recombinants place the HP locus within a 16-cM interval between markers D7S495 and D7S688. This confirms the localization of HP to 7q reported in a separate French kindred (2).

Chromosome Mapping↗
PubMed1996

Recurrent duplication and deletion polymorphisms on the long arm of the Y chromosome in normal males.

Deletion of the 50f2/C (DYS7C) locus in interval 6 of Yq has previously been reported as a polymorphism in three males. We describe a survey of worldwide populations for further instances of this deletion. Of 859 males tested, 55 (approximately 6%) show absence of the 50f2/C locus; duplication of the locus was also detected in eight out of 595 males (approximately 1.4%). Populations having the deletion are confined to Asia, Australasia, and southern and northern Europe; of those of reasonable sample size, Finns had the highest deletion frequency (55%; n = 21). The deletions vary in size and the larger ones remove some of the RBM (RNA Binding Motif) genes, but none of the deletion males lack DAZ (Deleted in AZoospermia), a candidate gene for the azoospermia factor. On a tree of Y haplotypes, 28 deletion and eight duplication chromosomes fall into six and four haplotypic groups respectively, each of which is likely to represent an independent deletion or duplication event. Microsatellite and other haplotyping data suggest the existence of at least two further classes of deletion. Thus duplications and deletions in this region of Yq have occurred many times in human evolution, but remain useful markers for paternal lineages.

Asia↗
PubMed1996

Phenotypic variation in Waardenburg syndrome: mutational heterogeneity, modifier genes or polygenic background?

We have identified 11 mutational changes in the PAX3 gene in patients with type 1 Waardenburg syndrome (WS1) including three in the paired domain, six within or immediately adjacent to the homeodomain and two previously described polymorphic variants in exons 2 and 6. The affected members of one family carried substitutions involving two base pairs separated by one unaltered codon. Two of the deleterious mutations were identical and three others were identical to previously reported mutations. A comparison of clinical findings in families carrying substitutions in the same codon failed to reveal conspicuous similarities. Although subtle mutation-specific effects may well exist, allelic heterogeneity clearly cannot account for within family variation. However, the striking concordance of a pair of monozygotic twins with Waardenburg syndrome (WS) and previous reports of similar pairs indicate that phenotypic variation in WS has a genetic basis. If the genetic effects are mediated by oligogenic epistasis, as studies in the mouse suggest, it may ultimately be possible to predict clinically relevant aspects of the Waardenburg phenotype.

Amino Acid Sequence↗
PubMed1996

Partial trisomy 10 mosaicism with cutaneous manifestations: report of a case and review of the literature.

A female infant with partial trisomy 10 mosaicism and hypomelanosis of Ito is presented. Features include a prominent forehead, hypertelorism, large dysplastic ears, prominent nasal root, a cleft lip and alveolar ridge, bilateral metatarsus adductus, and streaks and whorls of hypopigmented skin. The skin findings were diagnostic for hypomelanosis of Ito. A peripheral blood karyotype was normal. Fibroblasts from a junctional skin biopsy revealed mosaicism for partial trisomy of chromosome 10 [46, XX/47, XX, +del(10) (q11.2q23.2)]. The physical findings of this patient are compared to five published cases of complete trisomy 10 mosaicism and 94 cases of isolated trisomy 10p and trisomy 10q.

Abnormalities, Multiple↗
PubMed1995

Interstitial deletion of the long arm of chromosome 6 associated with unusual limb anomalies: report of two new patients and review of the literature.

We report on unusual manifestations in 2 unrelated children with interstitial deletion of 6q, with nearly identical breakpoints of 6q16.2q23.1 and 6q16.3q22.3. Major findings include growth retardation, profound developmental delay, microcephaly, facial anomalies, sparse hair, congenital heart defects, and striking hand malformations. Discordant anomalies were duodenal atresia and hypoplastic genitalia in 1 child. Split-hand defect, polydactyly, gastrointestinal anomalies, and ectodermal dysplasia have not been described previously in children with 6q deletion. The presence of hand malformations in 2 children with similar deletion breakpoints strongly suggests that this is a candidate region for one or more genes involved in limb development. Comparison of the clinical findings of other patients with 6q2 deletion suggests a recognizable phenotype.

Chromosome Banding↗
PubMed1995

Strategies and logistical requirements for efficient testing in genetic disease.

Rapid advances in the field of human genetics have led to an increase in the availability of genetic diagnostic tests. This article reviews technical approaches and diseases for which metabolic, newborn screening, molecular, and cytogenetic diagnostic tests are available currently. Overlaps in areas of diagnostic testing that have emerged from the application of new technology in the field of genetics also are discussed, as are criteria and approaches used for identifying conditions for which diagnostic, presymptomatic, prenatal, and carrier testing should be offered. Finally, the delivery of these results and necessary genetic counseling that should accompany this information are reviewed.

Blotting, Southern↗
PubMed1994

Mechanism for transforming growth factor beta regulation of alpha mRNA in lipopolysaccharide-stimulated B cells.

Transforming growth factor (TGF)-beta has been shown to stimulate isotype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated B cells. The induction of isotype switching is associated with the appearance of novel germline alpha transcripts that cannot be found in cultures stimulated with LPS alone. TGF-beta also increases the steady state level of productive alpha mRNA. In order to further elucidate both the role of TGF-beta and germline transcripts in isotype switching to IgA in B cells, the mechanism responsible for the changes in alpha mRNA was investigated. The increase in alpha mRNA which does not occur until day 2 of culture continues until at least day 4. Nuclear run-on analysis demonstrated that TGF-beta does not significantly increase the rate of transcription of either germline or productive alpha mRNA after 12, 24, or 48 h of culture. However, by day 2 of culture TGF-beta increases the half-life of alpha mRNA. These findings support the idea that TGF-beta acts as a secondary signal to stimulate isotype switching to IgA in a population that has already received a signal that drives it toward IgA production. In addition these studies suggest that either the germline transcripts or processing of pre-germline alpha mRNA transcripts plays a role in targeting recombination.

Animals↗
PubMed1990

DNA haplotype analyses of patients with hyperphenylalaninemia.

Linkage analysis of phenylketonurics has shown a strong association between the DNA haplotype at the phenylalanine hydroxylase (PAH) locus and phenylketonuria (PKU). Similarly, a genetic linkage between less severe forms of hyperphenylalaninemia (HPA) and the PAH locus has been suggested. In the present study we analyzed this linkage in more detail. Haplotypes at the PAH locus were determined for 19 individuals with moderately elevated plasma phenylalanine and normal urinary neopterin/biopterin ratios. Fourteen of these individuals had plasma phenylalanine levels of 4-10 mg/dl (mild HPA), and the other five had plasma phenylalanine levels of 10-19 mg/dl (atypical PKU). Thirteen of the 15 HPA families consisted of an affected child and at least one other sibling. Elevated plasma phenylalanine was seen to genetically segregate with specific PAH alleles in each family. Summation of the LOD scores for both categories of moderate plasma phenylalanine elevation gave a maximum value of 3.556 at theta = 0. At theta = 0 this gives a probability of linkage between the PAH locus and the locus for moderate phenylalanine elevations that is approximately 3,600:1. None of the alleles segregating with either mild HPA or atypical PKU were of haplotype 2 or 3, and 13/20 were of types 1 or 4. This is in agreement with the most deleterious mutations being on haplotypes 2 and 3 and with the less severe mutations being on haplotypes 1 and 4. chi 2 Analyses indicated no statistically significant correlation between HPA and a particular haplotype or restriction-enzyme site.

Alleles↗
PubMed1989

Optimum radiation technique for retinoblastoma in conserved eyes.

The study evaluated 121 consecutive unoperated cases of retinoblastoma in children. They received radiation as the primary treatment for their ocular disease. The stage grouping was done according to Reese classification. Ninety four children had their disease evaluated by CT scan. All except one had imaged lesions in both eyes. In addition, twenty six had thickened optic nerves and twenty one showed chiasmal infiltration. Radiation field selection was based on clinical and CT imaged disease. A tumor dose of 4500c Gy in 16 to 19 fractions over 18 to 24 days was delivered by cobalt teletherapy. The target volume encompassed ora serrata anteriorly and optic chiasma posteriorly in all cases. Tumor response and patient survival was correlated with the initial stage and radiation factors utilised amongst them. Encouraging results were obtained using three field radiation technique with an open anterior field and a TDF between 75 and 90.

Child↗
PubMed1979

Smoking and gastric juice volume in outpatients.

The volumes and pH of gastric juice in 26 outpatients presenting for dental surgery were measured by simple aspiration through a nasogastric tube introduced after the induction of anaesthesia. The average volume in these patients who were non-smokers was 9 ml and in those patients who had smoked on the day of the operation was 19 ml. Four of the smokers had more than 25 ml of gastric juice with a pH of 2.0 or less. It is suggested that out-patients who smoke would benefit from prophylaxis such as oral antacids or metoclopramide before anaesthesia.

Adult↗
PubMedDate not supplied

Implications of molecular diagnostic testing in families with hereditary pancreatitis.

Hereditary Pancreatitis (HP), is an autosomal dominant trait, which presents with recurrent attacks of abdominal pain, and is the most common cause of chronic relapsing pancreatitis in children. In addition to recurring episodes of intense epigastric pain, patients have nausea, vomiting, and anorexia, and typically show elevated serum amylase levels during the acute episode that can rapidly decline in convalescence. Complications of long-standing disease include features of chronic pancreatitis, such as pancreatic pseudo-cyst, exocrine and endocrine failure, parenchymal calcification, and pancreatic cancer. A large family from Virginia, which was originally studied by Katwinkle and Lapey in 1973, was re-ascertained through a new proband. Linkage studies in this family mapped the gene to the 7q35 region, with similar results being reported simultaneously by two other groups. A pathogenic G to A transition mutation in exon 3 of the cationic trypsinogen (CT) gene, which had previously been mapped to this region, was found both in our family as well as other families from North America. Many other conditions can produce abdominal symptoms that are often mis-attributed to the disease in HP families. An affected member of our family in whom the mutation was confirmed by direct sequencing of exon 3 of the cationic trypsinogen gene requested diagnostic testing on his 4-year-old son because of onset of severe abdominal pain and vomiting. Screening for the mutation in this child did not reveal the pathogenic G to A change. These results prevented unnecessary invasive diagnostic procedures and treatment in this child. The pre-symptomatic testing of high risk individuals could, thus, have a significant impact on the well being of both affected and normal family members.

Adult↗
PubMedDate not supplied

Ultrasonic debridement of mitral calcification.

Dense annular calcification to the valve attachment is particularly hazardous during mitral valve replacement because of the difficulty of placing sutures and the risk of atrioventricular rupture. We report 11 patients who underwent decalcification of the mitral anulus with the Cavitron Ultrasound Surgical Aspirator (CUSA) during mitral valve replacement. This resulted in a greatly simplified suture placement and prosthetic valve seating as well as enlargement of the annular orifice. Four other patients underwent CUSA debridement of the anterior leaflet of the mitral valve during concomitant aortic valve replacement and CUSA debridement of the aortic anulus. There were no operative deaths or major complications. Ultrasonic debridement is a useful adjunct in the surgical management of the heavily calcified mitral valve.

Adult↗
PubMedDate not supplied

Fine mapping of the human biotinidase gene and haplotype analysis of five common mutations.

Biotinidase deficiency is an autosomal recessive defect in the recycling of biotin that can lead to a variety of neurologic and cutaneous symptoms. The disease can be prevented or effectively treated with exogenous biotin. The biotinidase locus (BTD) has been maped to 3p25 by in situ hybridization. The gene has been cloned, the coding region sequenced, the genomic organization determined, and a spectrum of mutations has been characterized in more than 90 individuals with profound or partial biotinidase deficiency. We have conducted haplotype analysis of 10 consanguineous and 39 nonconsanguineous probands from the United States and 8 consanguineous probands from Turkey to localize BTD with respect to polymorphic markers on 3p and to investigate the origins of five common mutations. The inbred probands were homozygous for overlapping regions of 3p ranging in size from 1.1 to 80 cM which were flanked most narrowly by D3S1259 and D3S1293. Radiation hybrids and haplotype analysis of markers within this region suggest that BTD is located within a 0.1-cM region flanked by D3S3510 and D3S1286. The radiation hybrid data suggest that the BTD gene is oriented 5' to 3' between the centromere and the 3p telomere. Association studies indicate that the gene is closer to a third locus D3S3613 than D3S3510, two markers which cannot be resolved by existing linkage data. The BTD locus and D3S3613 must therefore lie between D3S3510 and D3S1286. Comparison of haplotypes reveals evidence for possible founder effects for four of the five common mutations.

Adult↗
PubMedDate not supplied

Time course of changes in P-wave duration during exercise.

The exercise-induced increase in P-wave duration reported previously has not been studied on a minute-by-minute basis. We measured the P duration in 47 normal subjects and 43 coronary artery disease (CAD) patients each minute during an exercise test. We found that prolongation of the P wave in those with CAD occurs relatively early and the difference between normal subjects and CAD patients is greater near maximum exercise. The data suggest that an increase in P-wave duration may reflect an increase in the left-ventricular end-diastolic pressure and may occur earlier that ST-segment depression.

Coronary Disease↗