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G Tadini

Publications and source records attributed to G Tadini.

At least 19 recordsLinked to original sources
PubMed2006

Dystrophic epidermolysis bullosa pruriginosa in Italy: clinical and molecular characterization.

Dystrophic epidermolysis bullosa (DEB) pruriginosa (DEB-Pr) is a rare variant of DEB due to COL7A1 dominant and recessive mutations, which is characterized by severe itching and lichenoid or nodular prurigo-like lesions, mainly involving the extremities. Less than 30 patients have been described showing variable disease expression, and frequently, delayed age of onset. We report the clinical and molecular characterization of seven Italian DEB patients, three affected with recessive DEB-Pr and four with dominant DEB-Pr. In all the patients, the signs were typical of a mild DEB phenotype, until the onset of pruritus, which was followed by worsening of the clinical picture, with appearance of the distinctive lichenified lesions of DEB-Pr. Nine mutations were found in the COL7A1 gene, three of which were novel and one was de novo. DEB-Pr patients with either dominant or recessive mutations were shown to synthesize a normal or variably reduced amount of type VII collagen, which was correctly deposited at the dermal-epidermal junction. Since six of these mutations have been reported in DEB patients in the absence of intense pruritus, these data implicate a role of yet unidentified phenotype-modifying factors in the pathogenesis of DEB-Pr.

Adolescent↗
PubMed2004

Intracellular degradation of beta4 integrin in lethal junctional epidermolysis bullosa with pyloric atresia.

BACKGROUND: Junctional epidermolysis bullosa with pyloric atresia (PA-JEB) is a rare autosomal recessive genodermatosis that manifests with neonatal mucocutaneous blistering and gastric outlet obstruction. The disease, which is caused by mutations in the alpha6beta4 integrin genes (ITGA6, ITGB4), is usually lethal. However, nonlethal cases have also been reported. Mutation database analysis has suggested that premature termination codons predominantly result in lethal forms while missense mutations frequently associate with nonlethal variants. Nevertheless, it is becoming more and more evident that the disease phenotype is also influenced by the position of the mutation in the protein functional domains. OBJECTIVE: To investigate the molecular basis of a novel PA-JEB lethal case. METHODS: Reverse transcriptase-polymerase chain reaction and direct sequencing-based mutation screening were performed. Mutation consequences in the patient's keratinocytes were then analysed by Northern blot and immunoprecipitation. Immunofluorescence analysis of cultured keratinocytes treated with protein intracellular degradation pathway inhibitors was also carried out. RESULTS: The phenotype was caused by the presence, in the homozygous state, of a novel 33 bp in-frame deletion (nucleotides 175-207) in the ITGB4 coding sequence. Despite the normal steady-state level of integrin beta4 mRNA, the mutation, designated DeltaR59-A69, results in the almost complete absence of alpha6beta4 integrin in the patient's skin and cultured keratinocytes. Exposure of the patient's keratinocytes to the proteasomal inhibitor clasto-lactacystin beta-lactone increased the expression of the mutated beta4 integrin chains indicating that the proteasome complex is involved in the degradation of the internally deleted beta4 polypeptides. CONCLUSIONS: We report for the first time a homozygous in-frame deletion in the ITGB4 gene. Our results suggest that the deletion of amino acids R59-A69 interferes with the biosynthetic folding of the protein, leading to a rapid degradation of the mutated beta4 chains. These findings provide new insight into the pathogenic effects of mutations affecting different functional domains of the beta4 integrin molecule and their prognostic implications in PA-JEB patients.

Base Sequence↗
PubMed2001

Characterization of mutations leading to recessive dystrophic epidermolysis bullosa and Marfan syndrome in a single patient.

Dystrophic epidermolysis bullosa (DEB) is a rare genetic skin disorder. In this report we have investigated an Italian child affected with recessive DEB (RDEB) and demonstrated that he was homozygous for the mutation R226X in the type VII collagen gene (COL7A1), leading to absence of type VII collagen at the dermal-epidermal junction. There was no family history of inherited skin blistering but the child's father was affected by Marfan syndrome, an autosomal dominant connective tissue disorder that results from mutations in the fibrillin-1 gene (FBN1). Analysis of this gene showed that the RDEB patient and his father were both heterozygous for a novel FBN1 mutation, C1971Y. This mutation affects one of the six obligate cysteine residues within one of the calcium-binding epidermal growth factor-like regions of the protein. At the age of 2-years the RDEB patient showed signs of early aortic dilatation, suggesting that he is likely to develop a Marfan syndrome phenotype in the future. This is a unique case of these two coexisting inherited disorders.

Child, Preschool↗
PubMed2000

A -96C-->T mutation in the promoter of the collagen type VII gene (COL7A1) abolishing transcription in a patient affected by recessive dystrophic epidermolysis bullosa.

Hereditary dystrophic epidermolysis bullosa (DEB) refers to a group of clinically heterogeneous skin blistering diseases due to mutations in the collagen type VII gene (COL7A1). We report two novel mutations found in a patient affected by the most severe form of DEB, the recessive Hallopeau-Siemens variant (HS-RDEB): the R1978X nonsense mutation, in exon 72, and the -96C-->T transition, in the promoter region. The allele specific analysis of the transcripts from skin fibroblasts of the patient showed that the -96C-->T mutation is associated to the absence of collagen type VII (COLVII) mRNA. This mutation, the first one ever identified in the promoter of COL7A1, falls in an Sp1 motif, localized between nucleotides -96 and -91. Gel shift analysis indicated that the -96/-91 sequence is a functional Sp1 site and that the -96C-->T transition inhibits the binding of the trascription factor. These data indicate that the -96/-91 sequence is a crucial Sp1 site whose integrity is necessary for COL7A1 expression. The compound heterozygosity for the -96C-->T null mutation and for the R1978X mutation leads to the absence of COLVII at skin level and to the severe phenotype of the HS-RDEB patient. Hum Mutat 16:275, 2000.

Cells, Cultured↗
PubMed1999

Three homozygous PTC mutations in the collagen type VII gene of patients affected by recessive dystrophic epidermolysis bullosa: analysis of transcript levels in dermal fibroblasts.

The Hallopeau-Siemens variant of recessive dystrophic epidermolysis bullosa (HS-RDEB) is a severe inherited skin disease characterized by the absence of collagen type VII (COLVII) and anchoring fibrils (AF), caused by mutations in collagen type VII gene (COL7A1). Mutations leading to the formation of premature termination codons (PTCs) of translation are the characteristic genetic lesions in HS-RDEB patients; many PTC mutations have been found to be associated with a marked reduction or complete absence of COLVII mRNA. In this article, we report homozygosity for three different mutations in the COL7A1 of HS-RDEB patients. One mutation, the R2685X, falling in exon 109, is a novel mutation, whereas the other two, the 425A-->G falling in exon 3 and the 497insA in exon 4, have been previously identified in compound heterozygosity with different mutations in other unrelated RDEB patients. Haplotype analysis in three Italian families carrying the 497insA mutation suggested a common origin of this mutation and indicated that this is an ancestral Italian mutation. All these mutations generate PTCs and are associated with the absence of COLVII expression, as detected by immunofluorescence analysis of the patient's skin. Evaluation of the levels of the mutated COLVII mRNAs in cultured skin fibroblasts of the patients and of their parents showed that all the mutated transcripts were expressed at consistent levels. Therefore, our results indicate that a marked mRNA reduction is not a constant feature associated with PTC mutations in COL7A1.

Adolescent↗
PubMed1998

Phacomatosis pigmentokeratotica: report of new cases and further delineation of the syndrome.

BACKGROUND: The epidermal nevus syndromes include different diseases that have the common feature of mosaicism. One of these has been recently identified and named phacomatosis pigmentokeratotica, in analogy to phacomatosis pigmentovascularis. It is characterized by an organoid nevus with sebaceous differentiation, a speckled-lentiginous nevus, and other associated anomalies. It has been hypothesized that this syndrome is caused by a particular genetic mechanism known as the twin-spot phenomenon. OBSERVATIONS: We describe 3 patients manifesting an association of organoid nevus showing sebaceous differentiation and speckled-lentiginous nevus with associated anomalies and update the neurologic findings of a previously described patient. Hemiatrophy seems to be a common finding in all cases; hyperpathia, dysesthesia, and hyperhidrosis, as well as other neurologic defects, may be present. CONCLUSIONS: The findings in these patients allowed us to better delineate this syndrome. Further studies are needed to elucidate the underlying genetic defect. At present, however, the hypothesis that best explains this phenotype is twin spotting. Clinical recognition of this syndrome can contribute to the classification of the epidermal nevus syndromes and give insight into unusual genetic mechanisms occurring in humans.

Adolescent↗
PubMed1998

Localized peeling skin syndrome: case report with ultrastructural study.

We report a young woman in whom the history, clinical features, histopathological and ultrastructural findings led to a diagnosis of peeling skin syndrome (PSS). PSS is a rare and not well classified genodermatosis, mainly characterized by the spontaneous separation of the stratum corneum from the stratum granulosum. The unusual feature in our patient was the strict localization to the palm. PSS has been described as a more generalized disease frequently sparing palms and soles. We propose the diagnosis label of 'localized PSS' for this previously undescribed variant of a rare keratinization defect.

Adult↗
PubMed1998

Unusual hyperpigmentation developing in congenital reticular ichthyosiform erythroderma (ichthyosis variegata).

We present an unusual new clinical feature which developed in a patient with congenital reticular ichthyosiform erythroderma. This rare ichthyotic disorder is characterized by erythematous ichthyotic skin surrounding slowly enlarging areas of normal skin, and by a pathognomonic ultrastructural pattern, namely perinuclear deposits of a filamentous material in vacuolized keratinocytes. At the age of 18 years, a 23-year-old woman developed several irregular hyperpigmented macules on her limbs, which were almost black in colour. These lesions have not been observed in the other patients affected by the disease nor, to our knowledge, in other ichthyotic disorders. Electron microscopy and immunohistochemistry demonstrated that the lesions were strictly related to the ichthyotic skin and that their dark colour was especially due to melanosome accumulation in activated dendritic melanocytes. An unusual postinflammatory hyperpigmentation, in which the lack of pigment deposition in the keratinocytes is due to a transfer defect in pathological cells, is hypothesized. A characteristic hyperplastic stimulation of the epidermis is also taken into consideration to explain the lack of a similar picture in other erythrodermic ichthyotic disorders with a continuous inflammatory process.

Adult↗
PubMed1998

Hairy elbows.

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Child↗
PubMed1997

Family with "pure" hair-nail ectodermal dysplasia.

"Pure" ectodermal dysplasias are developmental disorders affecting only tissues of ectodermal origin. Two different pure ectodermal dysplasias involving only hair and nails have been described to date. Here we describe congenital nail dystrophy and hypotrichosis associated with folliculitis decalvans in a family suggesting autosomal-dominant transmission. This report documents peculiar clinical and ultrastructural hair findings that fit poorly into previously described conditions. Thus the reported patients could represent a new type of pure ectodermal dysplasia.

Adult↗
PubMed1997

A homozygous in-frame deletion in the collagenous domain of bullous pemphigoid antigen BP180 (type XVII collagen) causes generalized atrophic benign epidermolysis bullosa.

We report a missplicing event affecting the expression of bullous pemphigoid antigen BP180 (type XVII collagen) in a patient with generalized atrophic benign epidermolysis bullosa (GABEB). The segregation of the mutated allele in the family is consistent with the pathogenic role of the mutation. The homozygous mutation 2441-2A --> G disrupts a splice-site sequence in gene (BPAG2) for BP180 and results in an in-frame exon skipping within the collagenous ectodomain of the protein. The consequent deletion of 9 amino acids in the mutant BP180 is predicted to alter the structure of the homotrimer and is expected to exert a deleterious effect on stability of the protein that would account for the complete absence of immunoreactivity of the proband's skin to antibodies directed against BP180. These findings underscore the importance of structural integrity of the extracellular domain of BP180 for the stability of the protein.

Adult↗
PubMed1997

Epidermolysis bullosa pruriginosa.

Epidermolysis bullosa (EB) pruriginosa is a rare clinical subset of dystrophic EB, characterized by marked itching and presence of prurigo-like or lichenoid features. In order to further delineate the phenotype and understand the pathogenesis of this disorder, the clinical, histological and ultrastructural findings of a 19-year-old patient presenting a typical form of EB pruriginosa are described. The prevalence of papular itchy lichenoid lesions, signs of scratching and paucity of blisters at the time of clinical examination may result in incorrect diagnosis and treatment. Microscopic studies of the lesions show the typical findings of dystrophic EB associated with an unusually high density of collagen bundles and absence of elastic fibres in the upper dermis. Itching lichenoid lesions of EB pruriginosa could represent an abnormal dermal reactivity of some patients to their inherited bullous disorder.

Adult↗
PubMed1997

Ichthyosis congenita type IV: a new case resembling diffuse cutaneous mastocytosis.

The wide phenotypical heterogeneity within the ichthyosis congenita group of diseases is well known. We report a case of a very rare and unusual autosomal recessive ichthyosis congenita, type IV, according to the ultrastructural classification. Our case presented the triad clue for the diagnosis, characterized by follicular hyperkeratosis, prematurity and perinatal complications, but the clinical diagnosis was further complicated by hypereosinophilia and a strongly positive Darier's sign suggesting diffuse cutaneous mastocytosis. The diagnosis was provided only by electron microscopy, which showed the pathognomonic markers of ichthyosis congenita type IV, namely a large number of membrane structures in the stratum corneum and stratum granulosum. As a consequence, correct genetic counselling for the parents was carried out, and they were informed about the benign course of the disease after the complications of the perinatal period. This case is a further example of the reliability of ultrastructural markers in the diagnosis of inherited keratinization disorders, especially those with an unusual clinical appearance.

Humans↗
PubMed1996

Cardio-facio-cutaneous (CFC) syndrome: report of an adult without mental retardation.

We report on a 25-year-old woman with typical manifestations of the cardio-facio-cutaneous (CFC) syndrome, but without mental retardation. She had valvular and infundibular pulmonic stenosis, brittle and woolly hair with patchy alopecia, scant body hair, dry and hypohydrotic skin, and characteristic facial traits. To our knowledge, this is the first case of CFC syndrome without mental retardation but typical cutaneous findings.

Abnormalities, Multiple↗