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Reuven Bergman

Publications and source records attributed to Reuven Bergman.

48 records · Page 3Linked to original sources
PubMed2003

The handheld dermatoscope as a nail-fold capillaroscopic instrument.

BACKGROUND: The presence of nail-fold capillary abnormalities may be useful in diagnosing several connective tissue disorders, including scleroderma, dermatomyositis, and mixed connective tissue disease, and in differentiating primary Raynaud phenomenon from Raynaud phenomenon due to scleroderma and mixed connective tissue disease. Capillaroscopy, however, usually requires special equipment and may be time consuming. Purpose To investigate the potential use of the unmodified common handheld dermatoscope as a capillaroscopic instrument. Subjects The study included 106 patients who were consecutively referred and a control group of 170 healthy subjects or patients with unrelated skin disorders. METHODS: A nail-fold capillaroscopic examination using a standard handheld dermatoscope was performed on all fingers of each subject. A scleroderma-dermatomyositis pattern was defined as the presence of 2 or more of the following findings in at least 2 nail folds: enlargement of capillary loops, loss of capillaries, disorganization of the normal distribution of capillaries, "budding" ("bushy") capillaries, twisted enlarged capillaries, and capillary hemorrhages (extravasates). RESULTS: A scleroderma-dermatomyositis pattern was found in 19 (70.4%) of 27, 7 (63.6%) of 11, and 4 (50%) of 8 patients with scleroderma, dermatomyositis, and mixed connective tissue disease, respectively. These frequencies were statistically significantly higher than a null percentage of scleroderma-dermatomyositis pattern in the control group (P<.001) and a scleroderma-dermatomyositis pattern in only 1 (4.5%) of 22 patients with systemic lupus erythematosus as well as in 2 (5.3%) of 38 patients with Raynaud phenomenon but without evidence of a connective tissue disorder (P<.01). CONCLUSIONS: The capillaroscopic results obtained with the dermatoscope are comparable to those described with other instruments. Therefore, the unmodified hand-held dermatoscope may be used as a capillaroscopic instrument to detect a scleroderma-dermatomyositis pattern and to help the dermatologist in the clinical diagnosis of connective tissue disorders.

Adolescent↗
PubMed2003

Epidermolytic hyperkeratosis and epidermolysis bullosa simplex caused by frameshift mutations altering the v2 tail domains of keratin 1 and keratin 5.

The cytoskeleton of epithelial cells is formed by heteropolymeric keratin proteins characterized by a central alpha-helical rod flanked by nonhelical head and tail domains of variable sequence. Most mutations described in 18 distinct keratins disrupt highly conserved regions at the boundaries of the rod, which have been recognized as zones of overlap during keratin alignment and assembly into intermediate filaments. We recently reported the first mutation located in a keratin tail domain (V2) in ichthyosis hystrix Curth-Macklin. In this study, we report two novel frameshift mutations that are predicted to alter the tail of keratin 1 or keratin 5, leading to an atypical form of epidermolytic hyperkeratosis and a mild form of epidermolysis bullosa simplex, respectively. Mutation analysis of the patient with epidermolytic hyperkeratosis revealed a de novo heterozygous nucleotide insertion (1752insG) in exon 9 of KRT1, predicted to result in an aberrant 69 residue keratin 1 tail. In the patient with mild epidermolysis bullosa simplex, we identified a single nucleotide deletion (1635delG) in exon 9 of KRT5 leading to frameshift and translation of an abnormal V2 domain, 35 amino acids longer than the native keratin 5 tail. Our results, together with previous observations, establish the existence of a subgroup of keratin disorders due to frameshift mutations altering the keratin tail domains that are characterized by phenotypic heterogeneity.

Adolescent↗
PubMed2003

Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular dystrophy.

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by abnormal growth of scalp hair during infancy, and by the later occurrence of macular degeneration leading to blindness during the first to third decade of life. Hypotrichosis with juvenile macular dystrophy was recently shown to result from mutations in CDH3 encoding P-cadherin. In this study, we assessed 27 individuals, including nine patients, belonging to five families in an attempt to characterize further the CDH3 mutation spectrum and delineate possible phenotype-genotype correlations. Deleterious biallelic mutations, predicted to lead to the translation of a dysfunctional protein, were found in all affected individuals. Four of these mutations are novel. Affected individuals of two large separate apparently unrelated families of Arab Israeli origin were found to carry the same homozygous mis-sense mutation (R503H) in exon 11 of the CDH3 gene. This mutation, which alters a Ca2+-binding site in the fourth extracellular domain of P-cadherin, was previously described in a third unrelated Arab Israeli family. Using haplotype analysis for a series of polymorphic markers encompassing the CDH3 gene, we obtained evidence suggesting a founder effect for R503H in the Arab Israeli population. We also compared the dermatologic and ophthalmologic features of 22 hypotrichosis with juvenile macular dystrophy patients with known recessive mutations in CDH3. Whereas hair paucity and macular degeneration were found in all patients, we noticed significant interfamilial and intrafamilial differences in hair morphology, associated skin findings as well as severity and age of onset of visual disability. Altogether, our results obtained in a series of families of various ethnic origins firmly establish mutations in CDH3 as the proximal cause of hypotrichosis with juvenile macular dystrophy and demonstrate genetic homogeneity as well as phenotypic heterogeneity in this disorder.

Cadherins↗
PubMed2003

A comparative study of immunohistochemistry and electron microscopy used in the diagnosis of epidermolysis bullosa.

Electron microscopic examination still is the gold standard for classifying epidermolysis bullosa, although it is relatively expensive, time consuming, and not readily available. Immunoreagents have been developed recently to map antigens in the basement membrane on routinely processed specimens. The current study was performed to examine the diagnostic usefulness of immunohistochemistry, as compared with electron microscopic examination, for analyzing routine formalin-fixed paraffin-embedded sections of epidermolysis bullosa. This study investigated 39 consecutively diagnosed cases of epidermolysis bullosa in which both electron microscopic examination and immunohistochemistry were used. In each case, three monoclonal antibodies were used to stain for laminin 1, collagen IV, and keratin. The immunohistochemical patterns were defined as follows: epidermolysis bullosa simplex (laminin, collagen IV, or both at the dermal floor of the blister and keratin at both the dermal floor and the epidermal roof), junctional epidermolysis bullosa (laminin, collagen IV, or both at the dermal floor of the blister and keratin only at the epidermal roof), and dystrophic epidermolysis bullosa (collagen IV, laminin, or both, and keratin all at the epidermal roof). Altogether, electron microscopic examination subclassified epidermolysis bullosa into its three major forms in 37 of the 39 cases (95%), and immunohistochemistry in 33 of the 39 cases (85%). All of the classifiable cases were concordant. Specifically, immunohistochemistry was diagnostic in 10 of 14 (71%) epidermolysis bullosa simplex cases, 14 of 14 (100%) junctional epidermolysis bullosa cases, and 9 of 11 (82%) dystrophic epidermolysis bullosa cases. The most frequent cause for inconclusive immunohistochemical results was failure in staining of the basement membrane with the antibodies to both laminin and collagen IV. In conclusion, the use of immunohistochemistry on routinely processed specimens may be useful for subclassifying epidermolysis bullosa into its major forms in the majority of the cases, although it still cannot fully replace electron microscopic examination or immunofluorescence mapping in the diagnosis of epidermolysis bullosa.

Adolescent↗
PubMed2002

Human telomerase RNA component expression in Spitz nevi, common melanocytic nevi, and malignant melanomas.

BACKGROUND: Telomerase is a ribonucleoprotein DNA polymerase that is capable of synthesizing telomeres onto the ends of chromosomes. The cumulative loss of telomerase activity is believed to be associated with cell senescence. Telomerase activity has been shown to be higher in malignant melanomas than in common melanocytic nevi. The aim of the present study was to elucidate the pattern of expression of the human telomerase RNA (hTER) component in routinely processed specimens of Spitz nevi, malignant melanomas, and ordinary melanocytic nevi. METHODS: Ten specimens of each type of tumor were studied, using an in situ hybridization technique. RESULTS: All three types of tumors demonstrated moderate to high intensities of hTER expression, usually in more than half of the tumor cells, and the majority of the studied lesions in each group did not show stratification of staining. The hTER component was also detected in the epidermis, sweat glands, and pilosebaceous units. CONCLUSIONS: hTER levels do not necessarily correlate with the level of telomerase activity, and the level and pattern of hTER expression are not useful as an adjunct to the histologic differential diagnosis of Spitz nevi from melanocytic nevi and malignant melanomas.

Diagnosis, Differential↗
PubMed2002

Clinicopathologic reassessment of non-mycosis fungoides primary cutaneous lymphomas during 17 years.

BACKGROUND: New classification systems have recently been proposed for primary cutaneous lymphomas (PCLs). The aim of our study was to evaluate the applicability and significance of the new classification systems to the diagnosis and management of non-mycosis fungoides (non-MF) PCL. METHODS: Immunohistochemical restaining, histological reclassification, and clinical follow-up of all new non-MF PCL cases during 17 consecutive years were performed. The histological reclassification was performed according to the Revised European-American Lymphoma (REAL) classification, except for lymphomatoid papulosis (Lyp), which was included as an indolent lymphoma, according to the European Organization for the Research and Treatment of Cancer (EORTC) classification. RESULTS: During the period 1983-99, 251 new PCL cases were seen, 213 (85%) of which were MF and Sézary syndrome (eight cases), and 38 (15%) of which were non-MF. Of the latter, 20 (53%) were B-cell lymphomas, including eight (40%) follicle center lymphoma, follicular (FCLF), eight (40%) marginal zone lymphoma (MZL), two (10%) diffuse large cell lymphoma, and two (10%) unclassifiable cases. Most or all of the lesions did not stain for CD10, CD43, and bcl-2 protein, and immunostaining for kappa and lambda immunoglobulin light chain restriction was much more useful diagnostically in MZL. Of the 18 primary non-MF cutaneous T-cell lymphomas, 13 (72%) were Lyp, all of which were type A, four (22%) were CD30+ anaplastic large cell lymphoma, and one (6%) was natural killer (NK)/T-cell lymphoma. Except for the NK/T-cell lymphoma, all the other non-MF PCLs had an indolent course. CONCLUSIONS: A minority of the routinely diagnosed PCLs are non-MF, equally divided between B- and T-cell lymphomas. The REAL classification is applicable to the majority, although it does not include entities such as Lyp; the clinical correlations are not as obvious because most of the non-MF PCLs tend to have a relatively indolent course.

Adolescent↗
PubMed2002

A novel missense mutation affecting the human hairless thyroid receptor interacting domain 2 causes congenital atrichia.

Congenital atrichias represent a large and heterogeneous group of inherited hair disorders. In this report, we describe a patient affected with alopecia universalis congenita (MIM 203655). Sequence analysis revealed a G to A transition at cDNA position 3034 of the hairless hr gene present in a homozygous state in the patient and in a heterozygous state in the patient's mother, and absent in the patient's sister. The mutation is predicted to result in the substitution of an asparagine residue for an aspartate amino acid (D1012N) at a position previously shown in the rat to affect hairless binding to thyroid hormone receptor. This study presents the first evidence in humans for the functional importance of the hairless thyroid receptor interacting domain 2.

Adolescent↗
PubMed2002

A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy.

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by early hair loss heralding severe degenerative changes of the retinal macula and culminating in blindness during the second to third decade of life. Recently, we identified a frameshift mutation in the CDH3 gene encoding P-cadherin as the proximal cause of hypotrichosis with juvenile macular dystrophy in four families. We report here another consanguineous family in which four members were diagnosed with hypotrichosis with juvenile macular dystrophy. Light and scanning electron microscopy revealed in all patients morphologic hair shaft abnormalities consistent with pili torti. Ocular fundus examination disclosed marked degeneration of the macular pigment epithelium. Electrophysiologic studies were diagnostic for severe retinal dysfunction. DNA sequence analysis of the entire coding sequence of CDH3 revealed in all affected individuals a homozygous missense mutation resulting in a single amino acid substitution at position 503 of P-cadherin sequence (R503H). The mutation completely segregated with the hypotrichosis with juvenile macular dystrophy phenotype in the family but was not detectable in 83 healthy, unrelated controls. The amino acid substitution affects a highly conserved residue and is predicted to alter a Ca2+ binding domain of P-cadherin. This is the first pathogenic missense mutation reported in CDH3 and the second mutation found to underlie hypotrichosis with juvenile macular dystrophy. Our data establish recessive mutations in CDH3 as the molecular cause of hypotrichosis with juvenile macular dystrophy and expand our understanding of the pathophysiology of this intriguing disorder.

Amino Acid Sequence↗
PubMed2002

Junctional epidermolysis bullosa in the Middle East: clinical and genetic studies in a series of consanguineous families.

BACKGROUND: Junctional epidermolysis bullosa (JEB) is a group of inherited blistering diseases characterized by epidermal-dermal separation resulting from mutations that affect the function of critical components of the basement membrane zone. This group of autosomal recessive diseases is especially prevalent in regions where consanguinity is common, such as the Middle East. However, the clinical and genetic epidemiology of JEB in this region remains largely unexplored. OBJECTIVE: The aim of the present study was to assess a series of consanguineous JEB families originating from the Middle East. METHODS: We identified 7 families referred to us between 1998 and 1999 and originating from the United Arab Emirates, Saudi Arabia, Sudan, Yemen, and Israel. Histologic, immunofluorescence, and electron microscopy studies were performed to direct the subsequent molecular analysis. DNA obtained from all family members was amplified by means of polymerase chain reaction and analyzed by conformation-sensitive gel electrophoresis with subsequent direct sequencing. RESULTS: In 6 families presenting with the clinical and histologic features distinctive for JEB, mutations in genes encoding 1 of the 3 subunit polypeptides of laminin-5 were identified. Two families each had mutations in LAMB3, 2 in LAMA3, and 2 in LAMC2. Out of 7 distinct mutations, 5 were novel and 2 were recurrent. No relationship was found between the presence of nonsense/frameshift mutations in laminin-5 genes and perinatal mortality, contradicting a major genotype-phenotype correlation previously reported in the European and US literature. Similarly, none of the recurrent LAMB3 hot spot mutations previously described in other populations was found in our series. Finally, in a family with the clinical diagnosis of generalized atrophic benign epidermolysis bullosa, a homozygous non-sense mutation in Col17A1 gene (encoding the BPAG2 antigen) was identified. CONCLUSION: The present report suggests (1) the existence of a unique spectrum of mutations in the Middle East populations and (2) the need for the implementation of a diagnostic strategy tailored to the genetic features of JEB in this region.

Autoantigens↗
PubMedDate not supplied

Bullous pemphigoid in two young infants.

Bullous pemphigoid (BP) usually affects the elderly. The disease is uncommon in children and only a few cases have been described in infants < or =4 months of age. We describe two infants, ages 3 and 4 months, with BP. One infant had a recalcitrant course, and responded only to a combination of high-dose oral corticosteroids and dapsone.

Dapsone↗