Giuseppe Del Porto

Granulomatous slack skin: Cytogenetic and molecular analyses

Granulomatous slack skin (GSS) is a rare disorder which is considered a slowly evolving T-cell lymphoma associated with granulomatous inflammation that mediates clastolysis. A combined cytogenetic, molecular, and cellular analysis was conducted on a clinically and histologically defined case of GSS. Cell cultures obtained from the skin biopsy showed trisomy of chromosome 8, and the DNA sample extracted from the skin biopsy showed a T-cell receptor beta-chain rearrangement.

Autosomal-dominant Retinitis Pigrnentosa Associated with an Arg-135-Trp Point Mutation of the Rhodopsin Gene: Clinical Features and Longitudinal Observations

Purpose: To report the clinical and functional characteristics of patients affected with autosomal-dominant transmitted retinitis pigmentosa (adRP) from a large Italian pedigree in which a point mutation predicting the Arg-135-Trp change of rhodopsin was identified by polymerase chain reaction-single-strand conformation polymorphism analysis. Methods: Seven patients, ranging in age from 6 to 41 years, underwent a full clinical ophthalmologic evaluation, kinetic visual field testing, and electroretinographic testing. Results: In agreement with previous reports, this rhodopsin mutation yielded a particularly severe phenotype, both clinically and functionally. The evaluation of patients from this pedigree in the first and second decade of life demonstrated that retinal function is still electroretinographically measurable at least until 18 years of age, although reduced to 2% to 4% of normal. Longitudinal measures showed that the rate of progression of the disease was unusually high, with an average 50% loss per year of electroretinographic amplitude and visual field area with respect to baseline. Later in the course of the disease, macular function is also severely compromised, leaving only residual central vision by the fourth decade of life. Conclusions: The phenotype associated with mutations in codon 135 of the rhodopsin molecule appears to have an unusually high progression rate and yields an extremely poor prognosis. These distinctive features make the Arg-135-Trp phenotype substantially different from the general RP population, and also from many of the other adRP pedigrees with known rhodopsin mutations reported to date. Ophthalmology 1996,-103:1443-1452

Inv dup(15): contribution to the clinical definition of phenotype

One of the primary goals in medical genetics is a precise clinical definition of chromosomal diseases. This is now possible because of the increased number of case reports and new techniques. A male patient, without a clear‐cut syndrome, was cytogenetically investigated. Chromosomal analysis showed a small unidentified bisatellited supernumerary marker. In situ hybridization with a biotin‐labeled DNA probe for the chromosome 15 centromere (D15Z1) demonstrated that the marker was derived from chromosome 15. Hybridization with the Prader‐Willi Syndrome Cosmid biotinylated probe (localized to band 15q11‐q13) showed a signal on both ends suggesting a marker with a symmetrical inv dup(15) and a breakpoint localized in q13. It was then possible to define the karyotype as: 47,XY,+ inv dup(15) (pter‐q13::q13‐pter). All cases of inv dup(15) reported in the literature were reviewed, paying particular attention to the different breakpoints involved, in order to provide a better clinical definition of this syndrome.

Cytogenetic follow-up in a case of Sézary syndrome

A cytogenetic follow-up study was performed for a 3-year period on a 70-year-old patient with Sézary syndrome (SS). The results showed formation of hypotetraploid cell clones with 60 to 89 chromosomes and 19 markers, some of which appeared during the period of study and stabilized thereafter. The incidence of these clonal cells increased from 29% to 85% during the follow-up study. The results confirm the presence of hypotetraploid cell clones, especially in the more advanced stages of SS. Moreover, some marker chromosomes in our patient (M2 and M3), derived from chromosome 2, were similar to those observed in SS by other investigators. According to our data and to those in the literature, SS appears to involve preferentially chromosomal regions 2p12-13, 2p21-22, 2q37, 17p13, 13q1, 9q11, 10p13, 14q11, 14q32, 7p1 and, to a lesser extent, 5q and 6q.

Clinical heterogeneity of dominant optic atrophy: the contribution of visual function investigations to diagnosis

Abstract• Background: The variability of the visual function impairment in dominant optic atrophy (DOA) makes it difficult to diagnose the disease within genealogies. Physiologic investigations were conducted on a family with DOA to evaluate methods of detecting clinical and subclinical signs in obligate heterozygotes, in order to identify affected subjects within the genealogy and to formulate the individual and reproductive risks • Methods: Investigations included tests for color vision, contrast sensitivity function (CSF), kinetic and static computerized perimetry, transient pattern reversal visual evoked potentials (VEPs) and steady-state flash VEPs • Results: Eight subjects from the pedigree were diagnosed as having DOA. Two of them were unaware of their affection, and six showed wide clinical variability. CSF paralleled the central visual impairment, but was also slightly impaired in the two unaware subjects. Static computerized perimetry disclosed mild sensitivity defects in the central visual fields in these two patients. VEPs showed heteregeneous results as well, ranging from normal findings to severely altered tracings • Conclusions: This investigation suggests that combined clinical and functional evaluation is necessary to diagnose DOA. Particularly, the combined use of computerized perimetry, CSF, and VEPs allowed the identification of cases at a subclinical stage.

Clinical Features of Autosomal Dominant Retinitis Pigmentosa Associated with the GLY-188-ARG Mutation of the Rhodopsin Gene

Several different rhodopsin gene mutations have been identified in the last years in pedigrees with autosomal dominant retinitis pigmentosa (adRP). In view of the differences in the molecular nature and location of these mutations, defining the phenotype has become increasingly important in order to identify the clinical counterpart to the different functional abnormalities of the photopigment molecule.1–9

Lentigo maligna: Cytogenetic, ultrastructural, and phenotypic characterization of a primary cell culture

Lentigo maligna is an early cutaneous neoplastic lesion. This article presents the cytogenetic, ultrastructural, and phenotypic characterization of a primary cell culture obtained from a patient affected with lentigo maligna. Two cellular clones were identified, both characterized by chromosomal markers involving chromosome 10 with a breakpoint at 10q26.

A male patient with 48,XXYY syndrome: importance of distinction from Klinefelter's syndrome

The authors report a patient affected with mental retardation, dysarthria, bilateral testicular hypoplasia and extensive ulcers of the lower limbs. Clinical study and laboratory tests revealed 48,XXYY syndrome. The authors confirm the importance of differential diagnosis from Klinefelter syndrome, illustrating the parameters and the pathology of both syndromes. They discuss the hypotheses concerning the pathogenesis of the ulcerations, and stress the importance of clinical and genetic characterization, leading to a differentiated prognosis of social capacity and prospect of working.

Pericentric inversion of chromosome 19 in three families.

SummaryPericentric inversion of chromosome 19 has been found in several members of three unrelated families from a restricted geographical region. In one of the families, an additional pericentric inversion of chromosome 9 was observed. Reproductive problems, multiple abortions in two families and a neonatal death in the third, were present. A review of previously described cases is included, and the genetic risk connected with this type of rearrangement is also discussed.

Trisomy 20 in a papillary urothelial carcinoma of the ureter

To contribute to the knowledge on tumorigenesis and the evolution of urothelial carcinoma of the ureter, we analyzed the clinical, histological, and cytogenetic aspects of a case. Primary cell cultures obtained from tumor specimens showed a trisomy of chromosome 20 where the c-src proto-oncogene, already described in literature as having an important role in the etiology and progression of some tumors, is located. In our case trisomy 20 is the only present marker and for this reason we think that it could play a role in the tumorigenesis of the urothelial carcinoma of the ureter.