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- Gånemo, Agneta, et al.
(författare)
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Autosomal recessive congenital ichthyosis in Sweden and Estonia: clinical, genetic and ultrastructural findings in eithty-three patients
- 2003
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Ingår i: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 83:1, s. 24-30
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Tidskriftsartikel (refereegranskat)abstract
- Congenital (non-bullous) ichthyosis is a rare group of keratinizing disorders which can be tentatively subclassified based on clinical criteria, analysis of transglutaminase 1 gene mutations and electron microscopy of epidermis. We studied 83 patients who were all on topical therapy and in 16 cases also on oral retinoids. Three main groups of patients were distinguished: (A) those with transglutaminase 1 gene mutations (n=44), (B) those without transglutaminase 1 gene mutations showing a coarse, generalized scaling (n=19), and (C) those without transglutaminase 1 gene mutations showing only fine or focal scaling (n=20). On clinical scoring, patients in group A were more hyperkeratotic and less erythematous than those in group B (p < 0.05). Anhidrosis was recorded in nearly all patients (> or = 80%), but ectropion and a collodion phenotype at birth were more common in group A versus other groups. Ultrastructurally, a high frequency of type I (Anton-Lamprecht's classification) was found in all three groups (37-63%), 20 cases of type II in group A and a few cases of types III and IV in groups B and C, respectively. In conclusion, transglutaminase 1 gene mutation is a major cause of congenital ichthyosis in Sweden and Estonia, and is often associated with severe scaling and ultrastructural type II in corneocytes. The transglutaminase-unrelated cases are more heterogeneous, probably reflecting a more varied aetiology.
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| 2. |
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| 3. |
- Pigg, Maritta, et al.
(författare)
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Haplotype association and mutation analysis of the transglutaminase 1 gene for prenatal exclusion of lamellar ichthyosis
- 2000
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Ingår i: Prenatal Diagnosis. - 0197-3851 .- 1097-0223. ; 20:2, s. 132-7
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Tidskriftsartikel (refereegranskat)abstract
- Lamellar ichthyosis (LI) is an autosomal recessive keratinization disorder of the skin. Genetic heterogeneity has been shown for the disease and there is evidence for the involvement of the transglutaminase 1 (TGM1) gene on chromosome 14q11. We have previously identified chromosome 14q11 haplotypes associated with ichthyosis in the Norwegian population. In this paper we describe antenatal exclusion of ichthyosis in two Norwegian families by chromosome 14q11 haplotype association and direct mutation analysis. In one pregnancy, the 11-week old fetus at risk for LI was found to share only one disease-associated haplotype. A subsequent mutation analysis of the TGM1 gene in fetal DNA revealed that the fetus carried a novel 3795A-->T transversion. The affected proband was compound heterozygous for the mutations 3795A-->T and 3239G-->C resulting in an Asp430Val and a Val379Leu, respectively. In another LI family, the 11-week old fetus was found to be heterozygous for the 14q11 haplotype associated with the disease. Subsequent mutation analysis revealed that the fetus was heterozygous for the 2526A-->G transition in the splice site of intron 5 whereas the proband was homozygous for the same mutation. Our results show that haplotyping can be a useful tool for prenatal diagnosis in diseases with genetic heterogeneity.
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| 4. |
- Pigg, Maritta
(författare)
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Molecular genetic studies of three autosomal recessive disorders : Sjögren-Larsson syndrome, glutathione synthetase deficiency and congenital ichthyosis
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Investigations at the DNA level were performed in order to characterise the molecular basis forthree genetic disorders:Sjögren-Larsson syndrome (SLS) is characterised by congenital ichthyosis and severeneurological symptoms. Linkage analysis and allelic association of 24 Swedish families affectedby SLS showed linkage between the disease and the marker D17S805 on chromosome 17. The distance between the marker D17S805 and the SLS gene was calculated to 0.6 cM or approximately 600 kb.Glutathione synthetase (GS) deficiency may be characterised by 5-oxoprolinuria,metabolic acidosis, haemolytic anaemia and sometimes central nervous system damage. Ninepatients with severe GS deficiency were sequenced for mutations in the GS gene onchromosome 20. Thirteen different missense mutations were found, of which 10 are novel.Expression studies of four engineered mutations confirmed the pathogenicity.Congenital ichthyosis (IC) is a heterogeneous group of recessive skin disorders includinglamellar ichthyosis (LI) & congenital ichthyosiform erythroderma (CIE). LI and CIE patientsfrom 43 Norwegian families were investigated for mutations in the TGM1 gene. A single splicesite mutation (2526A→G) in intron 5 was found on 80% of LI and CIE alleles of IC type I andII. Prenatal diagnosis based on chromosome 14q11 haplotyping were performed in twoNorwegian LI/CIE families and revealed one disease associated and one normal haplotype in thefoetuses of both families. Subsequent mutation analysis confirmed the results. We analysed LIand CIE patients from 28 Swedish families for mutations in the TGM1 gene. A missensemutation resulting in Ser358Arg and the splice site mutation 2526A→G were found on 52% ofalleles. Thirteen additional mutations were found of which nine are novel. Three individualsaffected by non-lamellar, non-erythrodermic ichthyosis were characterised for mutations in theTGM1 gene. Three mutations were found of which two are novel. The corresponding aminoacid substitutions result in a relatively mild IC phenotype.
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