1/180. Selective antibody deficiency to bacterial polysaccharide antigens in patients with netherton syndrome.Three patients with netherton syndrome, recurrent sinopulmonary infections, and humoral immune deficiency are described. Although quantitative serum immunoglobulin levels were generally normal, two patients had selective antibody deficiency to bacterial polysaccharide antigens, one associated with IgA-IgG-2 deficiency. A third patient had an antibody deficiency to protein antigens. This is the first report, to our knowledge, that describes antibody deficiency in patients with netherton syndrome. This finding demonstrates the importance of evaluating functional antibody responses to both protein and bacterial polysaccharide antigens and not relying on IgG subclass determination.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
2/180. Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 gaucher disease.gaucher disease is an autosomal recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal hydrolase, acid beta-glucosidase. Three phenotypically distinct subtypes result from different acid beta-glucosidase mutations encoding enzymes with absent or low activity. A severe neonatal type 2 variant who presented with collodion skin, ichthyosis, and a rapid neurodegenerative course had two novel acid beta-glucosidase alleles: a complex, maternally derived allele, E326K L444P, and a paternally inherited nonsense mutation, E233X. Because the only other non-pseudogene-derived complex allele, D140H E326K, also had the E326K lesion and was reported in a mild type 1 patient with a D140H E326K/K157Q genotype, these complex alleles and their individual mutations were expressed and characterized. Because the E233X mutation expressed no activity and the K157Q allele had approximately 1% normal specific activity based on cross-reacting immunologic material (CRIM SA) in the baculovirus system, the residual activity in both patients was primarily from their complex alleles. In the type 1 patient, the D140H E326K allele was neuroprotective, encoding an enzyme with a catalytic efficiency similar to that of the N370S enzyme. In contrast, the E326K L444P allele did not have sufficient activity to protect against the neurologic manifestations and, in combination with the inactive E233X lesion, resulted in the severe neonatal type 2 variant. Thus, characterization of these novel genotypes with non-pseudogene-derived complex mutations provided the pathogenic basis for their diverse phenotypes.- - - - - - - - - - ranking = 7keywords = gene (Clic here for more details about this article) |
3/180. Specific skin lesions occurring in a patient with Hodgkin's lymphoma.A 47-year-old man presented with a several month history of non-specific acquired ichthyosis, an unknown period of generalized lymphadenopathy and a short history of erythematous papules and nodules affecting the cutaneous drainage area of his right axillary lymph nodes. histology confirmed these lesions to be specific lesions of Hodgkin's lymphoma; that is, metastatic retrograde lymphatic spread from his axillary lymph nodes of CD30 , CD15 , reed-sternberg cells as well as mononuclear Hodgkin's cells. This is the most common site and mode of spread of Hodgkin's disease to the skin. As is typical of advanced Hodgkin's disease, as evidenced by specific cutaneous involvement, this patient died shortly after definitive diagnosis was made.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
4/180. A syndrome of congenital ichthyosis, hypogonadism, small stature, facial dysmorphism, scoliosis and myogenic dystrophy.Rud syndrome formerly was considered as a genetically heterogeneous but distinct clinical entity with the manifestations of ichtyosis, hypogonadism, small stature, mental retardation, epilepsy and, infrequently, retinitis pigmentosa. The existence of such a syndrome has recently been dismissed based on a new understanding of the ichthyoses. We report on the clinical history of a 14-year-old boy with congenital ichthyosis, small stature, hypogonadism, facial dysmorphism, nystagmus, kypho-scoliosis and myogenic dystrophy. He was diagnosed as Rud syndrome but developed neither seizures nor mental retardation. However a cousin was mentally retarded. The ichthyosis was familial as five relatives had ichthyosis but no other features of Rud syndrome. The patient had a deletion of the steroid-sulfatase gene. He had neither chondrodysplasia punctata, nor kallmann syndrome, two conditions which are part of the contiguous gene syndrome of the Xp22.3 region. Most case reports previously reported as Rud syndrome can now be reassigned under a contemporary ichthyosis classification that does not include Rud syndrome as a distinct entity. This case was clearly distinct from refsum disease, sjogren-larsson syndrome and any of the other ichthyosis disorders that have been suggested as a replacement for Rud syndrome. Thus the case reported here appears distinct from any previously described, currently recognized syndrome.- - - - - - - - - - ranking = 2488.6673367537keywords = contiguous gene syndrome, gene syndrome, contiguous gene, retardation, mental retardation, gene (Clic here for more details about this article) |
5/180. ichthyosis bullosa of siemens: report of a family with evidence of a keratin 2e mutation, and a review of the literature.We report a large family with ichthyosis bullosa of siemens (IBS) including eight affected members spanning three generations. The classical features of the disease were consistently observed with blistering, superficial peeling of the skin, and localized lichenified hyperkeratosis mainly confined to the limbs. Phenotypic variation, however, was also observed with some individuals exhibiting unusual clinical features. Specifically, the index patient was erythrodermic at birth; she subsequently developed a widespread pustular eruption. Erythroderma is classically absent in IBS and pustulation is very unusual. She also had hypertrichosis of the limbs, as did an affected female first cousin. This has not previously been reported in IBS. Electron microscopy showed complex aggregates of keratin in the spinous and granular layers associated, in places, with remarkably little cell lysis. Sequencing of genomic dna revealed a mutation (E493K) in keratin 2e. A review of the literature on IBS indicates that E493K is the most commonly reported mutation to date and might represent a mutational hotspot for this disease.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
6/180. Severe, non X-linked congenital microcephaly with absence of the pyramidal tracts in two siblings.In two siblings (a female and a male neonate), severe microcephaly, bilateral absence of the pyramids, severe hypoplasia of the cerebral peduncles, and dysplasia of the inferior olives was found together with microphthalmia, facial malformations and multiple contractures of the extremities. In both cases, the cerebral hemispheres otherwise showed a more or less normal gyral pattern with the insula incompletely covered by the opercula, and a tom but otherwise intact corpus callosum. In case 2, congenital cataract was also observed. The present cases can be characterized as a rapidly fatal, familial syndrome, probably transmitted as an autosomal recessive trait, and have several features in common with the Neu-Laxova syndrome. They differ in having a less severe form of microcephaly, a rather normal cytoarchitecture of the cerebral cortex, an apparently normal corpus callosum, no gross cerebellar abnormalities, and no other organ malformations. The present cases belong to a group of heterogeneous syndromes which have microcephaly, ocular and facial malformations, multiple contractures, and ichthyosis-like skin in common.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
7/180. Ichthyosis follicularis with alopecia and photophobia in a mother and daughter.A mother and daughter having ichthyosis follicularis with alopecia and photophobia (IFAP) are reported, with histopathological and electron microscopic findings. We have followed the clinical course of the mother for 26 years since she was 5 years old, and the daughter since birth. They have had almost all the classical and some of the minor symptoms of IFAP, including severe photophobia, extensive non-inflammatory follicular hyperkeratosis, generalized non-scarring alopecia, hyperkeratosis of the extensor aspect of the four extremities, nail deformity and recurrent cheilitis. In addition, their facial appearance greatly resembles that of previously reported patients. A consistent feature in the mother was florid keratotic inflammatory eruptions on the genital region during each of her pregnancies, which rapidly improved after the delivery. skin biopsy of the genital lesion showed marked acanthosis with dyskeratosis and spongiotic changes. The electron microscopic examination of diseased skin showed damaged desmosomes with spongiosis. No obvious changes were found in normal appearing skin.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
8/180. Type 2 gaucher disease: the collodion baby phenotype revisited.The association of gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase (EC 3.2.1.45), and congenital ichthyosis was first noted a decade ago. Subsequently, a null allele type 2 Gaucher mouse was generated that also exhibited ichthyotic skin, confirming that the skin disorder and enzyme deficiency were directly related. This paper details the clinical and molecular characterisation of 6 cases of type 2 gaucher disease presenting with the collodion baby phenotype. The identified mutant glucocerebrosidase alleles include two novel mutations (S196P and R131L) and two rare point mutations (R120W and R257Q), as well as alleles resulting from recombination with the nearby glucocerebrosidase pseudogene. There is significant genotypic heterogeneity in this rare subset of patients with type 2 gaucher disease. gaucher disease should be considered in the differential diagnosis of congenital ichthyosis in the newborn period.- - - - - - - - - - ranking = 3keywords = gene (Clic here for more details about this article) |
9/180. Hot spot mutations in keratin 2e suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of siemens.ichthyosis bullosa of siemens (IBS) is a rare disorder of cornification characterized by blister formation in the upper suprabasal layers of the epidermis. Molecular analysis of IBS has identified mutations in the keratin 2e (K2e) gene, which is located in the type II keratin gene cluster on chromosome 12q. We have studied two IBS families and have identified heterozygous point mutations in codon 493 of the K2e gene in both families. Whereas a non-conservative amino acid substitution at position 117 of the 2B region of K2e (E117K) was associated with a severe phenotype in family 1, family 2 showed mild clinical features as a result of a conservative substitution (E117D). These data suggest a phenotype-genotype correlation in these families.- - - - - - - - - - ranking = 3keywords = gene (Clic here for more details about this article) |
10/180. A case of ichthyosis linearis circumflexa successfully treated with topical tacrolimus.We report a case of ichthyosis linearis circumflexa (ILC) without the typical atopic manifestations and deformities of the hair shaft. The patient responded positively to treatment with topical tacrolimus, suggesting that abnormalities in the immunoregulatory mechanism may be involved in the pathogenesis of ILC.- - - - - - - - - - ranking = 1keywords = gene (Clic here for more details about this article) |
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