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A Pandya

Publications and source records attributed to A Pandya.

At least 37 records · Page 2Linked to original sources
PubMed2001

Fine mapping of a gene responsible for regulating dietary cholesterol absorption; founder effects underlie cases of phytosterolaemia in multiple communities.

Sitosterolaemia (also known as phytosterolaemia, MIM 210250) is a rare recessive autosomal inherited disorder, characterised by the presence of tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. The defective gene is hypothesised to play an important role in regulating dietary sterol absorption and biliary secretion, thus defining a molecular mechanism whereby this physiological process is carried out. The disease locus was localised previously to chromosome 2p21, in a 15 cM interval between microsatellite markers D2S1788 and D2S1352 (based upon 10 families, maximum lodscore 4.49). In this study, we have extended these studies to include 30 families assembled from around the world. A maximum multipoint lodscore of 11.49 was obtained for marker D2S2998. Homozygosity and haplotype sharing was identified in probands from non-consanguineous marriages from a number of families, strongly supporting the existence of a founder effect among various populations. Additionally, based upon both genealogies, as well as genotyping, two Amish/Mennonite families, that were previously thought not to be related, appear to indicate a founder effect in this population as well. Using both homozygosity mapping, as well as informative recombination events, the sitosterolaemia gene is located at a region defined by markers D2S2294 and Afm210xe9, a distance of less than 2 cM.

Arteriosclerosis↗
PubMed2001

Transpupillary thermotherapy (TTT) for age-related macular degeneration.

PURPOSE: To review the results of transpupillary thermotherapy (TTT) on choroidal neovascular membranes associated with age-related macular degeneration (AMD). MATERIALS AND METHODS: 35 eyes of 35 patients with AMD and choroidal neovascularization and exudation were treated with TTT and had fundus photographs and fluorescein angiography (FA) before and at least six months after TTT. 28 eyes had predominantly occult lesions as seen on FA, while 7 demonstrated primarily classic lesions. All were treated with 650mw power or less using the 810 nm diode laser (3000 micron spot, duration of 60 seconds). Visual acuity, lesion size, and amount of subretinal fluid were determined by results of examination and review of photographs and fluorescein angiograms. RESULTS: A 50% reduction in subretinal fluid was achieved in 67% of treated eyes overall, with stabilization of vision (less than three lines of visual acuity lost) in 86%. Complications from treatment were infrequent (9%) and involved hemorrhage noted in the region of treatment upon follow-up. CONCLUSION: TTT promotes resolution of subretinal fluid and appears to stabilize visual acuity in patients with exudative AMD.

Choroidal Neovascularization↗
PubMed2001

Expression and penetrance of the hereditary pancreatitis phenotype in monozygotic twins.

BACKGROUND: Hereditary pancreatitis (HP) is a rare autosomal dominant disorder with variable expression and an overall lifetime penetrance of 80%. We hypothesised that (1) monozygotic twins within similar environments would develop the typical signs of HP at a similar age, and (2) if penetrance were due to modifier genes or environment, all twin pairs would be concordant for expression of HP. AIM: Identify monozygotic twins with HP and determine the penetrance, concordance, and age of onset of symptoms. METHODS: Twins from HP kindreds were identified from the Midwest Multicenter Pancreatic Study group database, referrals, and literature searches. Each twin set was assessed for phenotypic expression, concordance, and difference in age of phenotypic onset of pancreatitis. The difference in onset of symptoms for symptomatic affected non-twin sibling pairs as well as non-twin pairs that were mutation, sex, and age matched were calculated as two comparison groups. RESULTS: Seven of 11 monozygotic pairs identified were suitable for evaluation and four were concordant for pancreatitis. Forty eight affected sibling pairs and 33 pairs of mutation, sex, and age matched (cationic trypsinogen R122H (30 pairs) and N29I (three pairs)) subjects were identified for comparison groups. The median (quartiles Q1, Q3) difference in the age of phenotypic onset in the concordant twins was 1 (0, 2.4) years, 2 (1, 6) for the affected siblings, and 7 (2, 15) years in the comparison control group. Three of the seven sets of twins (43%) were discordant for phenotypic expression of pancreatitis. The overall penetrance in the seven pairs of monozygotic twins was 78.6%. CONCLUSIONS: Genetic and/or environmental factors contribute to expression and age of onset of HP. Nuclear genes or general environmental factors alone cannot explain the 80% penetrance. Determining the mechanism of non-penetrance may help in developing a strategy to prevent the phenotypic expression of pancreatitis in individuals with an underlying genetic predisposition.

Adolescent↗
PubMed2000

Fluorescence in situ hybridization detectable mosaicism for Angelman syndrome with biparental methylation.

We present a child with mild to moderate global developmental delay including severe speech impairment, inappropriate happy demeanor, wide-based gait, frequent ear infections with mild hearing loss, deep-set eyes, a wide mouth, widely-spaced teeth, normal head circumference, and no seizures. Results of peripheral blood lymphocyte chromosomal analysis with GTG banding were normal. However, fluorescence in situ hybridization (FISH) studies showed mosaicism for a deletion of probes (D15S10 and SNRPN) from the Angelman syndrome (AS) critical region with approximately 40% of peripheral lymphocytes having the deletion. The deleted chromosome 15 also showed centromeric duplication, which was detected with a D15Z1 probe [46,XX, dic(15)(pter-->q11.1::p11.2-->q11. 1::q13-->qter)]. The same duplication pattern was observed in 30% of the nuclei obtained from a buccal smear. Methylation studies using polymerase chain reaction with sodium bisulfite-treated DNA demonstrated a normal biparental methylation pattern. To the best of our knowledge, this is the first case with AS and a FISH detectable deletion in a mosaic pattern. We recommend FISH studies for the detection of mosaicism in the patients with AS clinical findings even if results of the methylation studies are normal.

Angelman Syndrome↗
PubMed2000

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Africa, Northern↗
PubMed2000

Relation between choice of partner and high frequency of connexin-26 deafness.

Recessive mutations at the connexin-26 gene locus are now recognised as the cause of nearly half of all cases of genetic deafness in many populations. We suggest that this high frequency is only seen in populations with a long tradition of intermarriage among deaf people. Available data are consistent with the hypothesis that such marriages might well have contributed to the high frequency of connexin-26 deafness in the USA, and could represent a novel mechanism for maintaining specific genotypes at unexpectedly high frequencies.

Connexin 26↗
PubMed2000

MSY2: a slowly evolving minisatellite on the human Y chromosome which provides a useful polymorphic marker in Chinese populations.

We present the second human Y-specific minisatellite, MSY2 (DYS440). It consists of three or four copies of a 99-110bp repeat unit and is located about 1kb upstream of the DBY gene. The most common allele contains four units, but a three-unit allele has arisen on at least four occasions; in chimpanzees and orangutans, MSY2 contains only two units. It is therefore evolving slowly and provides a particularly useful polymorphic marker for Chinese populations.

Alleles↗
PubMed2000

A polymorphic L1 retroposon insertion in the centromere of the human Y chromosome.

We have identified a novel polymorphic L1 retroposon insertion, designated LY1, in the centromeric alphoid array of the human Y chromosome. The element belongs to the transpositionally active Ta subset and its presence is compatible with normal centromere function. It was found at highest frequency in China, where it accounts for 23% of the Han sample, and was present at low frequencies in the surrounding areas, but was not found at all outside Asia. Chromosomes carrying LY1 show considerable microsatellite diversity, suggesting an ancient origin for the lineage at approximately 10 000 years ago (with wide confidence limits), but only limited subsequent migration.

Base Sequence↗
PubMed2000

Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss.

Mutations in the GJB3 gene encoding connexin31 (Cx31) can cause a dominant non-syndromic form of hearing loss (DFNA2). To determine whether mutations at this locus can also cause recessive non-syndromic deafness, we screened 25 Chinese families with recessive deafness and identified in two families affected individuals who were compound heterozygotes for Cx31 mutations. The three affected individuals in the two families were born to non-consanguineous parents and had an early onset bilateral sensorineural hearing loss. In both families, differing SSCP patterns were observed in affected and unaffected individuals. Sequence analysis in both families demonstrated an in-frame 3 bp deletion (423-425delATT) in one allele, which leads to the loss of an isoleucine residue at codon 141, and a 423A-->G transversion in the other allele, which creates an Ile-->Val substitution at codon 141 (I141V). Neither of these two mutations was detected in DNA from 100 unrelated control subjects. The altered isoleucine residue lies within the third conserved alpha-helical transmembrane domain (M3), which is critical for the formation of the wall of the gap junction pore. Both the deletion of the isoleucine residue 141 and its substitution to valine in the two families could alter the structure of M3, and impair the function of the gap junction. The present data demonstrate that, like mutations in connexin26, mutations in Cx31 can lead to both recessive and dominant forms of non-syndromic deafness.

Adult↗
PubMed2000

Myelocystocele-cloacal exstrophy in a pedigree with a mitochondrial 12S rRNA mutation, aminoglycoside-induced deafness, pigmentary disturbances, and spinal anomalies.

A large Filipino-American family with progressive matrilineal hearing loss, premature graying, depigmented patches, and digital anomalies was ascertained through a survey of a spina bifida clinic for neural crest disorders. Deafness followed a matrilineal pattern of inheritance and was associated with the A1555G mutation in the 12S rRNA gene (MTRNR1) in affected individuals as well as unaffected maternal relatives. Several other malformations were found in carriers of the mutation. The proband had a myelocystocele, Arnold-Chiari type I malformation, cloacal exstrophy, and severe early-onset hearing loss. Several family members had premature graying, white forelock, congenital leukoderma with or without telecanthus, somewhat suggestive of a Waardenburg syndrome variant. In addition to the patient with myelocystocele, two individuals had scoliosis and one had segmentation defects of spinal vertebrae. The syndromic characteristics reported here are novel for the mitochondrial A1555G substitution, and may result from dysfunction of mitochondrial genes during early development. However, the mitochondrial A1555G mutation is only rarely associated with neural tube defects as it was not found in a screen of 218 additional individuals with spina bifida, four of whom had congenital hearing loss.

Aminoglycosides↗
PubMed2000

Annular abscesses in surgical endocarditis: anatomic, clinical, and operative features.

BACKGROUND: The aim of this study was to determine patterns of anatomic, clinical, and operative features in surgical endocarditis (SE) with annular abscess (AA). METHODS: The study consisted of a retrospective analysis of SE cases with AA between 1981 and 1997. RESULTS: A total of 41 cases with AA were found in 106 consecutive SE cases. There was a higher incidence of AA in aortic (37 of 71 [52%]) (p<0.01) compared to mitral (6 of 42 [14.3%]) or tricuspid (0 of 12) infections. However, the mitral abscesses had a greater tendency toward fistula or pseudoaneurysm formation (4 of 6 [67%]) than other valve abscess cavities (7 of 46 [15%]) (p<0.01). Severe heart failure (p<0.01), heart block (p<0.05), and fistula/pseudoaneurysm (p<0.001), were more often found in SE with AA than without. There were 46 separate aortic AA in 37 instances of aortic valve SE. Of these, 31 of 46 (67%) were less than 1 cm (group 1), 10 of 46 (22%) were large but confined to a given cusp annulus (group 2), 4 of 46 (8.6%) were large between multiple cusps (group 3), and 1 of 46 (2.2%) was circumferential (group 4). There were four instances of aortoventricular discontinuity. Group 1 abscesses were repaired by local closure without a patch significantly more often than the other groups. The mortality of SE with AA was significantly greater for larger AA (groups 3 and 4, 3 of 5 [60%]) than for smaller AA (groups 1 and 2, 0 of 36) (p<0.001). There were six separate mitral AA in six instances of mitral SE, five requiring patch repair. The 30-day operative mortality for AA cases was 3 of 41 (7.3%) compared to 2 of 65 (3.1%) without AA. All AA mortalities involved large AA in the aortic valve position. Of 35 mechanical valves placed for AA, only one required subsequent removal for prosthetic endocarditis. CONCLUSIONS: Annular abscesses are most frequent in aortic AA, but fistulas/pseudoaneurysms are more frequent in mitral AA. Small to moderate aortic AA can be managed by local closure without an increased mortality compared to SE without AA. Patients with large aortic AA have a higher operative mortality. Mechanical prostheses are safe and effective for the majority of patients with AA.

Abscess↗
PubMed2000

Validation of a multiplex methylation-sensitive PCR assay for the diagnosis of Prader-Willi and Angelman's syndromes.

BACKGROUND: Prader-Willi (PWS) and Angelman's (AS) syndromes are two distinct clinical entities caused by alterations in an identical but differentially methylated region of DNA on chromosome 15q. Highly complex laboratory tests are required for diagnosis because the disorders are caused by several genetic mechanisms. Methylation-specific PCR (MSPCR) is a relatively simple alternative method to detect the methylation status of the PWS/AS region. METHODS AND RESULTS: DNA was treated with sodium bisulfite, with alterations to the published method in which a neutralization step after the alkali treatment of the modified DNA enabled the use of the modified product directly in the PCR, eliminating the need for ethanol precipitation. Multiplex MSPCR using primers to methylated and unmethylated DNA was optimized to yield equal amplification efficiency for both products. Complete concordance was observed during the clinical validation of 40 previously characterized samples, except for one patient with mosaic AS detected by fluorescence in situ hybridization. CONCLUSION: We have developed and validated a multiplex MSPCR assay with alterations of the original published protocol that is technically robust and reproducible and can be used as a screening assay to detect PWS and AS.

Angelman Syndrome↗
PubMed2000

Drain fixation made foolproof.

A reliable method of securing drain tubing is presented. Knots made from two half-hitches have been used in the sailing world for many years. They provide a strong, slip-free knot which is simple to learn, tie, teach and easy to remove.

Drainage↗
PubMed1999

Longitudinal assessment of adaptive and maladaptive behaviors in fragile X males: growth, development, and profiles.

As young fully mutated fragile X [fra(X)] males age, cognitive levels (IQ scores) and adaptive behavior levels (DQ scores) decline. Given the variable behavioral profiles reported previously, we wondered whether changes in specific attributes of adaptive behavior are related to declines in composite adaptive behavior levels. We also examined maladaptive behavior to determine if changes are related to age. Therefore, we evaluated three areas of adaptive behavior, as well as maladaptive behavior, in 28 fully mutated fra(X) males, ages 4-14 years. To develop a profile of adaptive behavior, we analyzed nine subscale scores from the Vine-land Adaptive Behavior Scale (VABS). To assess maladaptive behavior, we graded part I of the VABS Maladaptive Behavior Scale. Subjects were sorted into three age cohorts, according to their initial test age: younger than 6 years; 6 to 9 years; older than 9 years. Results indicate that, in all age groups, the communications domain is the most severely impacted compared with either the socialization domain or daily living skills and that, in all age groups, the socialization domain is a relative strength compared with either the communications domain or daily living skills. The youngest cohort manifested significant increases in age-equivalent community living skills. Significant differences in age-equivalent scores between cohorts were observed in written language and play skills. Maladaptive behavior scores were available from cross-sectional data only. Twenty males (74%) showed significantly higher maladaptive scores than expected from other children their age. Our data analysis also revealed a moderate and significant negative correlation between maladaptive behavior levels and age (r = -0.54; P < 0.01). Curiously, adaptive and maladaptive behaviors did not correlate with each other.

Adaptation, Psychological↗
PubMed1999

Age-related language characteristics of children and adolescents with fragile X syndrome.

In addition to moderate-to-severe mental retardation (MR), the fragile X [fra(X)] mutation produces significant impediments in speech and language. Severe delays in speech and language have been demonstrated in both adult males and young individuals with the fra(X) mutation. Having observed longitudinal declines in IQ scores in young males with fra(X) and given the relationship between cognitive ability and language skill, we wanted to determine whether speech-language deficits in young males with fra(X) were age-related in ways comparable with those observed in cognitive deficits. We examined a small sample (n = 16) of children and adolescents, ages 6-17 years, using the Clinical Evaluation of Language Fundamental-Preschool (CELF-P). The CELF-P is used to evaluate language deficits in preschool children and assesses receptive and expressive language ability. It is standardized for children ages 3-7 years and provides age-normed standard scores. To evaluate changes in language scores, we converted raw scores into age-equivalents. Results indicate that males with fra(X) have significantly lower age equivalent scores compared with females. A cross-sectional analysis of males' age-equivalent scores reveals that a plateau is reached at approximately 48 months. Our findings suggest that, as with IQ and adaptive behavior scores, language development in young, fully mutated fra(X) individuals appears to reach a plateau as they age.

Adolescent↗
PubMed1999

Effect of optical digitizer selection on the application accuracy of a surgical localization system-a quantitative comparison between the OPTOTRAK and flashpoint tracking systems.

Application accuracy is a crucial factor for stereotactic surgical localization systems, in which space digitization camera systems are one of the most critical components. In this study we compared the effect of the OPTOTRAK 3020 space digitization system and the FlashPoint Model 3000 and 5000 3D digitizer systems on the application accuracy for interactive localization of intracranial lesions. A phantom was mounted with several implantable frameless markers which were randomly distributed on its surface. The target point was digitized and the coordinates were recorded and compared with reference points. The differences from the reference points represented the deviation from the "true point." The root mean square (RMS) was calculated to show the differences, and a paired t-test was used to analyze the results. The results with the phantom showed that, for 1-mm sections of CT scans, the RMS was 0.76 +/- 0. 54 mm for the OPTOTRAK system, 1.23 +/- 0.53 mm for the FlashPoint Model 3000 3D digitizer system, and 1.00 +/- 0.42 mm for the FlashPoint Model 5000 system. These preliminary results showed that there is no significant difference between the three tracking systems, and, from the quality point of view, they can all be used for image-guided surgery procedures.

Equipment Design↗