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G Pescia

Publications and source records attributed to G Pescia.

At least 19 recordsLinked to original sources
PubMed1997

Kerato-epithelin mutations in four 5q31-linked corneal dystrophies.

Granular dystrophy Groenouw type I (CDGG1), Reis-Bücklers (CDRB), lattice type I (CDL1) and Avellino (ACD) are four 5q31-linked human autosomal dominant corneal dystrophies. Clinically, they show progressive opacification of the cornea leading to severe visual handicap. The nature of the deposits remains unknown in spite of amyloid aetiology ascribed to the last two. We generated a YAC contig of the linked region and, following cDNA selection, recovered the beta ig-h3 gene. In six affected families we identified missense mutations. All detected mutations occurred at the CpG dinucleotide of two arginine codons: R555W in one CDGG1, R555Q in one CDRB, R124C in two CDL1 and R124H in two ACD families. This suggests, as the last two diseases are characterized by amyloid deposits, that R124 mutated kerato-epithelin (the product of beta ig-h3) forms amyloidogenic intermediates that precipitate in the cornea. Our data establish a common molecular origin for the 5q31-linked corneal dystrophies.

Alternative Splicing↗
PubMed1997

Frequency and impact of autosomal dominant polycystic kidney disease in the Seychelles (Indian Ocean).

BACKGROUND: As little such data is available in African populations, we investigated the prevalence of ADPKD and the impact of the disease in the Seychelles islands, where approximately 65% of the population is of African descent and 30% of Caucasian or mixed descent. METHODS: Prevalent cases were identified over a 3-year period by requesting all the doctors in the country (most of them are employed within a national health system) to refer all presumed or confirmed cases and by systematically examining the family members of all confirmed cases. The diagnosis was based on standard criteria including ultrasonographic findings and family history. RESULTS: Forty-two cases were identified in this population of 74,331 inhabitants, a total prevalence (per 100,000 total population) of 57 (95% CI, 41-76). All but one of the cases were of Caucasian descent so that the prevalence rates of the disease in the populations of Black and Caucasian descents were respectively 2 (0-11) and 184 (132-249). The prevalence rates of the gene(s) carriers were estimated to be 75 (45-117) in the total population respectively 6 (0-33) and 236 (140-372) in the Black and Caucasian populations. Haplotype analysis in 58 cases from three families showed a common DNA fragment in all affected individuals. Cases had significantly higher blood pressure compared to the general population and 21% had serum creatinine higher than 120 mumol/l. Among the established pedigrees, mean age of death between 1960 and 1995 (haemodialysis was introduced in 1992) was younger in subjects with than those without ADPKD (50.5 vs 67.7 years; P < 0.001). CONCLUSIONS: In the Seychelles, ADPKD clusters in the Caucasian population (possibly a founder effect), is rare in individuals of black descent, and is associated with substantial clinical and survival impact.

Adolescent↗
PubMed1997

Prognostic factors associated with loss of heterozygosity at the RB1 locus in retinoblastoma.

The nature of the tumorigenic mutation was analyzed in 30 retinoblastoma (Rb) tumors (16 non-hereditary and 14 hereditary) and categorized into loss of heterozygosity (LOH) or retention of heterozygosity (non-LOH) at the RB1 locus. These genotypic characteristics were compared with the clinicopathological phenotype for possible correlation. The overall frequency of LOH was roughly 55%, in both hereditary and non-hereditary Rb. The presence of LOH was preferentially associated with differentiated tumors and absence of choroidal invasion. LOH was found in 82% of females versus 33% of males. Finally, LOH-initiated tumors were associated with a significantly younger age at diagnosis in hereditary Rb. In conclusion, the preferential association of LOH with absence of choroidal invasion, tumoral differentiation, and younger age at diagnosis may establish LOH as a prognostic marker in Rb patients.

Biomarkers, Tumor↗
PubMed1997

A new case of Pfeiffer syndrome with mutation in FGFR2.

We report on a sporadic case of Pfeiffer syndrome in a male newborn with complex craniosynostosis, broad thumbs and great toes and early demise. SSCP and direct sequencing revealed a missense mutation at position 1037 of the exon B (or IIIc) of the FGFR2 gene (codon 342) resulting in a cysteine to serine modification (TGC-TCC). Genotype-phenotype correlations between the FGFRs mutations and the different craniosynostotic syndromes are discussed.

Acrocephalosyndactylia↗
PubMed1996

[Genetic counseling in oncology].

Some aspects of genetic counselling in cases with familial cancers is illustrated by use of 4 typical observations. By exact diagnosis and extended genealogic analysis the risk of consanguineous relatives may be estimated, if inheritance and genetic peculiarities of the particular disease are known. Predictive and presymptomatic testing should only be undertaken after thorough counselling. It should anyway be restricted to cases where preventive or curative measures are available.

Adenomatous Polyposis Coli↗
PubMed1996

[Retinoblastoma: clinical and molecular diagnostic aspects].

Retinoblastoma, a tumor of the immature retina concerns babies and young infants in particular. They make up for 14% of malignomas in the first years of life. There are two types of retinoblastoma: In the first two alleles of the gene Rb1 must be inactivated sequentially in the same retinoblast cell until this may escape control. In this case the retinoblastoma is always unilateral and unifocal. This is explained by the lower frequency of two mutations in one retinoblast. The other type, however, is inherited: One allele Rb1 is inactivated in all cells of the organism by mutation. The probability that a second mutation arrives in different retinoblasts is thus high. In this case bilateral multifocal tumors develop. Characterization of the Rb1 gene has permitted identification or at least determination of a haplotype in persons at risk. This knowledge is decisive for early recognition of babies at risk and for genetic counselling.

Child, Preschool↗
PubMed1996

Linkage of autosomal dominant radial drusen (malattia leventinese) to chromosome 2p16-21.

OBJECTIVE: To identify the chromosomal location of the gene involved in the pathogenesis of autosomal dominant radial drusen (malattia leventinese). PATIENTS: Eighty-six members of four families affected with radial drusen; one family of American origin and three families of Swiss origin. METHODS: Family members were clinically examined for the presence of radial drusen. Affected patients and potentially informative spouses were genotyped with short tandem repeat polymorphisms distributed across the autosomal genome. The clinical and genotypic data were subjected to linkage analysis. RESULTS: Fifty-six patients were found to be clinically affected. Significant linkage was observed between the disease phenotype and markers known to lie on the short arm of chromosome 2. The maximum two-point lod score (Zmax) observed for all four families combined was 10.5 and was obtained with marker D2S378. Multipoint analysis yielded a Zmax of 12, centered on marker D2S378. The lod-1 confidence interval was 8 cM, while the disease interval defined by observed recombinants was 14 cM. CONCLUSIONS: The gene responsible for autosomal dominant radial drusen has been mapped to the short arm of chromosome 2. This is an important step toward actually isolating the disease-causing gene. In addition, this information can be used to evaluate other familial drusen phenotypes such as Doyne's macular dystrophy for a possible allelic relationship.

Adolescent↗
PubMed1996

Sex mutation ratio in retinoblastoma and retinoma: relevance to genetic counseling.

PURPOSE AND METHOD: The parental origin of initial somatic and germline mutations (M1) in the retinoblastoma gene (RB1) was explored in 36 retinoblastoma (Rb) and 5 retinoma patients, of which 16 were presumably non-hereditary and 25 were hereditary. By this approach the male:female mutation ratio was determined by the gender quotient of mutation origin. RESULTS: The male to female mutation ratio in hereditary Rb was 19:2, which is consistent with a significant bias towards paternal origin of germline mutation. This ratio was of 5:2 in non-hereditary Rb which is not significant. DISCUSSION: Together with the published data, these results support a preferential paternal mutagenesis in hereditary Rb, but appear to reject paternal genomic imprinting at the RB1 locus as previously proposed in non-hereditary Rb. Genetic counseling in sporadic Rb may be substantially improved by the identification of the parental origin of initial mutation.

Cohort Studies↗
PubMed1996

Delineation of a 1-cM region on distal 5q containing the locus for corneal dystrophies Groenouw type I and lattice type I and exclusion of the candidate genes SPARC and LOX.

Granular Groenouw type I (CDGG1) and lattice type 1 (CDL1) corneal dystrophies are two distinct potentially blinding conditions. These two entities were recently mapped to a region on chromosome 5q. We have investigated 2 families of Swiss origin with CDGG1 and CDL1 by linkage analysis. Our data show a maximum lod score of 5.38 at theta = 0.00 for marker D5S393 in CDL1 and 4.17 at theta = 0.00 for D5S658 in CDGG1. When combined, these families show a maximum low score of 9.22 for D5S393 at theta = 0.00. This confirms previous reports. Furthermore, we describe a recombination centromeric to D5S399 in a member of the CDL1 family. Haplotype analysis in the 4 branches of the CDGG1 family demonstrated a common chromosomal region including D5S393 and D5S399 in all the affected members. By combining our data with previously reported mapping information and assuming that CDGG1 and CDL1 are allelic manifestations of the same gene, we can refine the location of the CDGG1/CDL1 gene to a 1-cM region on chromosome 5q. Using candidate genes in the 5q22-q32 interval, we investigated the possibility that mutations in the SPARC or LOX genes cause these corneal diseases. Several recombinations occurred between these two genes and CDGG1/CDL1 in our 2 families, thus excluding this hypothesis.

Alleles↗
PubMed1995

A sensitive enzyme immunoassay for pregnancy-associated plasma protein A (PAPP-A): a possible first trimester method of screening for Down syndrome and other trisomies.

Pregnancy-associated plasma protein A (PAPP-A) is a large glycoprotein produced mainly by the trophoblast during pregnancy and released into the maternal circulation. Its biological function is unknown. In the second trimester i.e. when Down syndrome (DS) screening is routinely performed, the level of maternal serum PAPP-A was found to be within the normal range in pregnancies affected by fetal trisomy 21. However, PAPP-A was shown to be a potent marker for DS before 14 weeks of gestation. Only radioimmunoassays (RIAs) based on labelled antigen competition reached the required sensitivity for early pregnancy PAPP-A determinations; but they have a very short shelf life due to inherent tracer half-life and, in the case of PAPP-A, instability of the labelled antigen after three weeks. We describe a convenient and novel enzyme immunoassay (ELISA) with high sensitivity and a long shelf life.

Abnormalities, Multiple↗
PubMed1995

[Clinical applications of molecular diagnosis of retinoblastoma ain 15 families].

PURPOSE: In 40% retinoblastoma (Rb) results from a hereditary mutation of the Rb susceptibility gene (RB1). In this study, we tested the usefulness of intragenic DNA analysis for ophthalmologic follow-up in affected families. METHODS: Molecular analysis was performed on 103 DNA samples of 15 Rb families. We used 7 intragenic polymorphic markers and one within the ESD gene for mutation linkage analysis. FINDINGS: DNA analysis was informative in 88% of relatives at risk of developing Rb. Among them, the presence of a mutated RB1 allele was excluded in 46%, while 29% were unaffected carriers and 25% had inherited the Rb predisposition. CONCLUSION: In the majority of familial Rb, the DNA analysis allows the identification of children carrying a RB1 mutation and who will need a close ophthalmologic follow-up under general anesthesia. When the mutated gene is absent, ophthalmological examination under narcosis is unnecessary. Finally, identification of asymptomatic carriers improve the accuracy of genetic counselling.

Adult↗
PubMed1995

Pregnancy-associated plasma protein A (PAPP-A): measurement by highly sensitive and specific enzyme immunoassay, importance of first-trimester serum determinations, and stability studies.

It has recently been established that maternal serum pregnancy-associated plasma protein A (PAPP-A) was reduced in pregnancies with fetal Down syndrome in the first but not in the second trimester of gestation. In comparison with two other placental proteins, human chorionic gonadotrophin and pregnancy-specific beta 1-glycoprotein, an explanation for this can be formulated based on the large molecular weight of PAPP-A. With the increasing clinical demand for fetal abnormalities to be diagnosed in the first rather than in the second trimester of pregnancy, maternal serum PAPP-A is a strong potential candidate for being used in routine trisomy screening. We have developed a sensitive enzyme immunoassay (ELISA) intended at smaller laboratories due to its long shelf life. Here we show that repeated freezing and thawing, or the addition of iodoacetate (5 mM) did not affect the results, at both high or low concentration of PAPP-A. It is also possible to introduce the serum into the test as a dry sample on blotting paper, easily posted in an envelope. A decrease of 21% was observed after such dry storage for three weeks at room temperature, which can be compensated for by the inclusion of a dried control serum, mailed with the sample(s).

Chorionic Gonadotropin↗
PubMed1994

Putative non-Mendelian transmission of retinoblastoma in males: a phenotypic segregation analysis of 150 pedigrees.

In a previous genotypic study of eight families, we described paternal segregation distortion favoring the transmission of mutant alleles at the retinoblastoma gene locus (RB1). In the current study, we reviewed all published retinoblastoma pedigrees with defined ascertainment (n = 150), to determine whether the phenotypic segregation frequency at the RB1 locus is in general influenced by the sex of the transmitting parent. Segregation analysis under complete ascertainment revealed that 49.1% of the offspring of male transmitters were affected, while 44.3% of the offspring of female transmitters were affected. While this difference is not statistically significant, it is consistent with the previous findings. No significant sex distortion could be detected among the progeny of carrier fathers and mothers. In order to quantify the transmission ratio more precisely further prospective molecular genetic analysis is warranted. We propose a biological mechanism to account for a putative segregation distortion, namely that genetic recombination creates clones of spermatogonia that are homozygous for the mutant RB1 allele leading to a non-Mendelian ratio of sperm. This model can be experimentally tested using amplification of DNA from single sperm cells.

Female↗
PubMed1994

Mid-term results with cultured epidermal autografts, allogenic skin transplants and cyclosporin A medication.

Transplantation of allogenic split thickness skin grafts (STSG) and immunosuppression with cyclosporin A enable early and definitive skin replacement of extensive, deep partial and full thickness burns. Covering burn defects with definitely engrafted, allogenic dermis and cultivated epithelial autografts (CEA) permits the subsequent withdrawal of cyclosporin A medication. Light-microscopy examination of biopsies, taken 12 and 24 months postgrafting, and electron microscopy of biopsies taken 12 months postgrafting, demonstrates a re-established, but somewhat reduced anchoring of the CEA as compared with a normal epidermal-dermal junction. Clinical inspection, 20 months postgrafting, confirms the histological observations that epifascial transplantation is qualitatively inferior to placing the allogenic STSG on the subcutaneous tissue. In the first situation, the dermis is inelastic and collagen deposition is excessive, whereas in the second case collagen deposition is comparatively reduced and the dermis shows clinically some elasticity.

Adult↗