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I Hausser

Publications and source records attributed to I Hausser.

At least 19 recordsLinked to original sources
PubMed2006

A founder mutation for ichthyosis prematurity syndrome restricted to 76 kb by haplotype association.

Autosomal recessive congenital ichthyosis (ARCI) is a group of keratinisation disorders that includes the ichthyosis prematurity syndrome (IPS). IPS is rare and almost exclusively present in a restricted region in the middle of Norway and Sweden, which indicates a founder effect for the disorder. We recently reported linkage of IPS to chromosome 9q34, and we present here the subsequent fine-mapping of this region with known and novel microsatellite markers as well as single nucleotide polymorphisms (SNPs). Allelic association, evaluated with Fisher's exact test and P (excess), was used to refine the IPS haplotype to approximately 1.6 Mb. On the basis of the average length of the haplotype in IPS patients, we calculated the age of a founder mutation to approximately 1,900 years. The IPS haplotype contains a core region of 76 kb consisting of four marker alleles shared by 97.7% of the chromosomes associated with IPS. This region spans four known genes, all of which are expressed in mature epidermal cells. We present the results from the analysis of these four genes and their corresponding transcripts in normal and patient-derived samples.

Alleles↗
PubMed2004

Alpha-1-antitrypsin deficiency alleles are not associated with cervical artery dissections.

The authors searched for the presence of alpha-1-antitrypsin (AAT) deficiency alleles PiZ and PiS in 74 patients with spontaneous cervical artery dissections (sCADs) and in 74 healthy control subjects. In both groups, the authors found four carriers of deficiency alleles. The connective tissue morphology of one additional patient with sCAD with PiZM genotype and her relatives was studied in skin biopsies. The PiZ allele did not segregate with morphologic alterations of the dermal connective tissue in the family. Therefore, AAT deficiency alleles may not play a role in the etiology of sCAD.

Adult↗
PubMed2004

[Repigmentation of persistent laser-induced hypopigmentation after tattoo ablation with the excimer laser].

Hypopigmented skin developed following tattoo removal with the Q-switched Nd:YAG laser. The hypopigmented area remained unchanged for over 4 years, until the use of the 308-nm xenon-chloride excimer laser induced a significant repigmentation in 40 sessions over 14 months. The excimer laser has the potential to influence the reduced activity of the melanocytes, as demonstrated with electron microscopy.

Adult↗
PubMed2004

Congenital muscular dystrophy with short stature, proximal contractures and distal laxity.

We report 5 cases (2 familial and 3 sporadic) who share a diagnosis of congenital muscular dystrophy (CMD) in association with short stature, proximal contractures, rigidity of the spine and distal joint laxity as well as early respiratory failure and mild to moderate mental retardation. The expression of collagen VI was confirmed to be normal on muscle biopsies of all 5 patients and in the informative family linkage to any of the three COL6 A loci was excluded. These findings extend the phenotypes within the CMD classification.

Adolescent↗
PubMed2002

Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos syndrome.

Skin hyperelasticity, tissue fragility with atrophic scars, and joint hypermobility are characteristic for the classical type of Ehlers-Danlos syndrome (EDS). The disease is usually inherited as an autosomal dominant trait; however, recessive mode of inheritance has been documented in tenascin-X-deficient EDS patients. Mutations in the genes coding for collagen alpha1(V) chain (COL5A1), collagen alpha2(V) chain (COL5A2), tenascin-X (TNX), and collagen alpha1(I) chain (COL1A1) have been characterized in patients with classical EDS, thus confirming the suspected genetic heterogeneity. Recently, we described a patient with severe classical EDS due to a Gly1489Glu substitution in the alpha1(V) triple-helical domain who was, in addition, heterozygous for a disease-modifying Gly530Ser substitution in the alpha1(V) NH(2)-terminal domain [Giunta and Steinmann, 2000: Am. J. Med. Genet. 90:72-79; Steinmann and Giunta, 2000: Am. J. Med. Genet. 93:342]. Here, we report on a 4-year-old boy with mild classical EDS, born to healthy consanguineous Turkish parents; the mother presented a soft skin, while the father had a normal thick skin. Ultrastructural analysis of the dermis revealed in the patient the typical "cauliflower" collagen fibrils, while in both parents variable moderate aberrations were seen. Mutation revealed the presence of a homozygous Gly530Ser substitution in the alpha1(V) collagen chains in the patient, while both parents were heterozygous for the same substitution. An additional mutation in either the COL5A1 and COL5A2 genes was excluded. Furthermore, haplotype analysis with polymorphic microsatellite markers excluded linkage to the genes coding for alpha3(V) collagen (COL5A3), tenascin-X (TNX), thrombospondin-2 (THBS2), and decorin (DCN). These new findings support further our previous hypothesis that the heterozygous Gly530Ser substitution is disease modifying and now suggest that in the homozygous state it is disease causing.

Amino Acid Substitution↗
PubMed2002

Sequence analysis of the COL5A2 gene in patients with spontaneous cervical artery dissections.

The authors searched for mutations in the gene that codes for the alpha2 chain of type V procollagen in 10 patients with spontaneous cervical artery dissections (sCAD). Two patients carried a missense mutation affecting the predicted C-propeptide (T1227S; D1429V). A third patient carried two mutations (V509A and P830L) in the same alpha2(V) chain. The T1227S mutation and the V509A/P830L haplotype also were detected among 50 healthy subjects. The D1429V substitution was detected neither in a series of 150 healthy control subjects nor among 50 additional patients with sCAD.

Amino Acid Sequence↗
PubMed2002

Genetic analysis of a severe case of Netherton syndrome and application for prenatal testing.

Netherton syndrome (NS) is a rare autosomal recessive disease with variable expression. It is defined by a triad of symptoms: congenital ichthyosiform erythroderma, trichorrhexis invaginata and atopy. Recently, genetic linkage has been established to the SPINK5 gene locus on chromosome 5q32 encoding the serine protease inhibitor LEKTI. In this study, we present a recurrent homozygous mononucleotide deletion (153delT) resulting in a severe case of NS exhibiting exfoliative erythroderma with lethal outcome at the age of 4 months and its application in prenatal testing in a subsequent pregnancy of the mother.

Carrier Proteins↗
PubMed2001

Pathogenesis of cervical artery dissections: association with connective tissue abnormalities.

BACKGROUND: The etiology of spontaneous cervical artery dissection (CAD) is largely unknown. An underlying connective tissue disorder has often been postulated. OBJECTIVE: To further assess the association of CAD with ultrastructural abnormalities of the dermal connective tissue. METHODS: In a multicenter study, skin biopsies of 65 patients with proven nontraumatic CAD and 10 control subjects were evaluated. The ultrastructural morphology of the dermal connective tissue components was assessed by transmission electron microscopy. RESULTS: Only three patients (5%) had clinical manifestations of skin, joint, or skeletal abnormalities. Ultrastructural aberrations were seen in 36 of 65 patients (55%), consisting of the regular occurrence of composite fibrils within collagen bundles that in some cases resembled the aberrations found in Ehlers-Danlos syndrome type II or III and elastic fiber abnormalities with minicalcifications and fragmentation. A grading scale according to the severity of the findings is introduced. Intraindividual variability over time was excluded by a second biopsy of the skin in eight patients with pronounced aberrations. Recurrent CAD correlated with connective tissue aberrations. In addition, similar connective tissue abnormalities were detected in four first-degree relatives with familial CAD. CONCLUSION: CAD is associated with ultrastructural connective tissue abnormalities, mostly without other clinical manifestations of a connective tissue disease. A structural defect in the extracellular matrix of the arterial wall leading to a genetic predisposition is suggested. The dermal connective tissue abnormalities detected can serve as a phenotypic marker for further genetic studies in patients with CAD and large families to possibly identify the underlying basic molecular defect(s).

Adult↗
PubMed2001

Generalized dystrophic epidermolysis bullosa: identification of a novel, homozygous glycine substitution, G2031S, in exon 73 of COL7A1 in monozygous triplets.

We report monozygous triplets affected with dystrophic epidermolysis bullosa (DEB). The female triplets were delivered by Caesarean section and skin fragility of each child, which was partly induced by trauma, was apparent from the third to fourth day of life. Clinically, the triplets were equally affected. Mutation analysis in this family revealed a novel recessively expressed glycine substitution, G2031S, in exon 73 of the collagen VII gene COL7A1. Most glycine substitutions in this gene region encoding for the triple helical domain of collagen VII are associated with milder, dominantly inherited phenotypes. By contrast, the novel point mutation of this study is clinically silent in the heterozygous state and leads to a severe DEB subtype when homozygous.

Collagen↗
PubMed2000

Mutations in the tropoelastin gene (ELN) were not found in patients with spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: The majority of patients with spontaneous cerebral artery dissection show ultrastructural alterations in dermal collagen and elastic fibers. METHODS: We studied the gene encoding tropoelastin (ELN) by reverse transcription-polymerase chain reaction and subsequent sequence analysis in 10 patients with abnormalities in their elastic fibers. RESULTS: No mutations were found in the whole coding region of the ELN gene. The simultaneous visualization and quantification of ELN splice variants by gene scanning enabled the analysis of the regulation of alternative splicing of ELN mRNA. No differences could be detected between fibroblast cultures of the patients and a control subject. CONCLUSIONS: Neither mutations in the ELN gene nor dysregulation of its activity appears to be the cause of the connective tissue disorder that is found in most patients with spontaneous dissections.

Adult↗
PubMed1999

[Restrictive dermopathy].

Restrictive dermopathy is a rare, fatal, autosomal recessive, congenital skin disease. Rigidity of translucent thin skin, which is thus highly vulnerable and tears, spontaneously causes intra-uterine fetal akinesia or hypokinesia deformation sequence (FADS), characteristic dysmorphic facies with fixed open mouth in O position, and generalized joint contractures (arthrogryposis). Polyhydramnios and pulmonary hypoplasia are distinctive manifestations, leading to respiratory insufficiency and premature delivery at about 31 weeks of gestation. We report on a case of a prematurely born infant who presented with the typical morphological features and describe the light- and electron-microscopical findings as described in the literature.

Abnormalities, Multiple↗
PubMed1999

Mutations in the COL5A1 coding sequence are not common in patients with spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: The dermal connective tissue of most patients with spontaneous cervical artery dissections (sCAD) contains abnormal collagen fibers. This suggests a predisposing connective tissue defect. The ultrastructural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patients to mutations within the genes encoding type V collagen. The aim of this study was to assess the alpha 1 chain of type V collagen (COL5A1) as a candidate gene for sCAD. METHODS: We searched for mutations in the COL5A1 gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational polymorphism analysis and nucleotide sequence analysis of polymerase chain reaction-amplified fragments of the whole COL5A1 coding sequence. RESULTS: We detected 1 missense mutation leading to a predicted amino acid (192D/N) substitution within the N-terminal propeptide in 2 siblings. All other patients showed regular COL5A1 sequences with some silent polymorphisms. CONCLUSIONS: Mutations in the COL5A1 gene do not appear to be a major factor in the etiology of sCAD.

Adult↗
PubMed1998

Ultrastructural connective tissue abnormalities in patients with spontaneous cervicocerebral artery dissections.

The cause of spontaneous cervicocerebral artery dissection is unknown. An underlying arteriopathy due to a connective tissue disorder has often been presumed. We studied 25 patients with proven nontraumatic dissections. The ultrastructural morphology of dermal connective tissue components was assessed by transmission electron microscopy of skin biopsies. Ultrastructural abnormalities were seen in 17 (68%) patients, resembling in some cases the aberrations found in Ehlers-Danlos syndrome type II or III. These observations indicate a correlation of cervical artery dissections with connective tissue abnormalities. A structural abnormality in the extracellular matrix potentially caused by basic molecular defects is suggested and warrants further exploration.

Adult↗
PubMed1998

[Comèl-Netherton syndrome].

The Comèl-Netherton syndrome is a rare autosomal recessive hereditary disease. A 23-year old female presented with the classical triad of ichthyosis linearis circumflexa, trichorrhexis invaginata with bamboo hairs of up to 12 cm length and atopic diathesis. Nevertheless, more than 20 years passed before the final diagnosis was established. In addition, the patient was slightly mentally retarded and suffered from a genital papillomatosis, minimal hypergammaglobulinaemia and a marked bilateral eyelid ectropion, more severe than previously reported. Oral therapy with Acitretin was quite successful.

Acitretin↗
PubMed1998

Acute bilateral renal vein thrombosis complicating Netherton syndrome.

UNLABELLED: A 1-year old male infant suffering from Netherton syndrome with severe generalized erythroderma presented with acute renal failure due to bilateral renal vein thrombosis (RVT) after a short episode of enteritis. The imperceptible fluid loss through the skin and the additional enteric water loss had led to decompensation of the delicate fluid balance and had resulted in RVT as a sequel of haemoconcentration. Reperfusion of the left kidney could be achieved by treatment with urokinase and heparin. Prophylactic oral anticoagulation was instituted for several weeks. CONCLUSION: In severe Netherton disease meticulous surveillance of the fluid balance is important and aggressive treatment is indicated in case of additional fluid loss.

Diagnosis, Differential↗