Search PubMed⌕ Search

Biomedical subjects

H Forsius

Publications and source records attributed to H Forsius.

At least 19 recordsLinked to original sources
PubMed2000

Mutations in KERA, encoding keratocan, cause cornea plana.

Specialized collagens and small leucine-rich proteoglycans (SLRPs) interact to produce the transparent corneal structure. In cornea plana, the forward convex curvature is flattened, leading to a decrease in refraction. A more severe, recessively inherited form (CNA2; MIM 217300) and a milder, dominantly inherited form (CNA1; MIM 121400) exist. CNA2 is a rare disorder with a worldwide distribution, but a high prevalence in the Finnish population. The gene mutated in CNA2 was assigned by linkage analysis to 12q (refs 4, 5), where there is a cluster of several SLRP genes. We cloned two additional SLRP genes highly expressed in cornea: KERA (encoding keratocan) in 12q and OGN (encoding osteoglycin) in 9q. Here we report mutations in KERA in 47 CNA2 patients: 46 Finnish patients are homozygous for a founder missense mutation, leading to the substitution of a highly conserved amino acid; and one American patient is homozygous for a mutation leading to a premature stop codon that truncates the KERA protein. Our data establish that mutations in KERA cause CNA2. CNA1 patients had no mutations in these proteoglycan genes.

Amino Acid Sequence↗
PubMed2000

Autosomal recessive cornea plana: in vivo corneal morphology and corneal sensitivity.

PURPOSE: Autosomal recessive corneal plana (RCP) is a rare corneal anomaly with unknown pathogenesis and a high incidence in Finland. The aim was to examine corneal sensitivity and the morphology of different corneal layers and subbasal nerves in RCP patients. METHODS: Three patients with a diagnosed autosomal recessive cornea plana were examined. Corneal sensitivity to different modalities of stimulation was tested in four corneas using noncontact esthesiometry. Tissue morphology of three corneas was evaluated, and in two corneas thickness of corneal layers was measured using in vivo confocal microscopy. RESULTS: Corneas of RCP patients appear to have mechanosensory, polymodal, and cold-sensitive nerve terminals. RCP patients had normal sensation thresholds for chemical, heat, and cold stimulation but a high threshold for mechanical stimulation. Their capacity to discriminate increasing intensities of stimulus was reduced, except for cold stimuli. Thickness of the epithelial layer was reduced, whereas total corneal and stromal thicknesses were slightly reduced or close to normal values. In all cases Bowman's layer was absent. Subbasal nerves had abnormal branching patterns. The arrangement of anterior keratocytes was altered, showing clustered and irregularly shaped nuclei. Increased backscattering of light in confocal microscopy through focusing (CMTF) profiles was observed throughout the stroma. Epithelial and endothelial cells appeared to be regular in shape. CONCLUSIONS: The present study revealed qualitative and quantitative alterations in corneal sensitivity, cellular morphology, and the thickness of corneal layers in RCP patients.

Cornea↗
PubMed1999

Skewed secondary sex ratio in the offspring of carriers of the 214G > A mutation of the RS1 gene.

Carriers of X-linked juvenile retinoschisis (RS) were previously suggested to give birth to an excess of boys. We determined the carrier status for the 214G > A mutation of the RS1 gene in 202 females belonging to a large RS founder pedigree. The secondary sex ratio (SSR) in the offspring of 149 carriers was 129.8 (z = 2.25), which differed significantly from that of the Finnish population (SSR 106) but not from that of 53 non-carrier females belonging to the same pedigree (SSR 116.7; z = 0.51). Since possible causes for the skewed SSR include factors affecting fertilisation, implantation and embryonic death, we searched for expression of RS1 in various placental and uterine cells and found that, in addition to the retina, RS1 is expressed in the uterus. We hypothesize that the RS1 protein has a role in implantation or embryonic survival.

Case-Control Studies↗
PubMed1999

Three widespread founder mutations contribute to high incidence of X-linked juvenile retinoschisis in Finland.

X-linked juvenile retinoschisis (RS) is a recessively inherited disorder causing progressive vitreoretinal degeneration in males. The gene defective in retinoschisis, XLRS1, has recently been identified and characterised. This gene consists of six exons encoding a protein with a putative role in cell-cell adhesion and phospholipid binding. Juvenile retinoschisis has been actively studied in Finland over the past 30 years, with over 300 diagnosed RS patients. Based on genealogical studies, approximately 70% of the Finnish RS patients originate from Western Finland and 20% from Northern Finland. In this study, one third of the known Finnish RS patients were screened for mutations of the XLRS1 gene. Haplotype analysis, using nine microsatellite markers spanning 1 cM in Xp22.2, suggested the segregation of eight different mutations in these families. To identify mutations, the six exons were amplified by PCR and analysed by single strand conformation analysis, followed by direct sequencing of the PCR products. We identified seven distinct missense mutations, all in exons 4 and 6. The mutations in exon 4, 214G > A and 221G > T, are accountable for RS in Western Finland. A third mutation in exon 4, 325G > C, gives rise to RS in Northern Finland. These three founder mutations are the predominant cause of RS in Finland and their existence explains the high incidence of the disease. The identification of mutations common in genetically isolated populations, such as Finland, allows the diagnosis of patients with an atypical RS phenotype and enables nationwide carrier testing and improved genetic counselling.

Adolescent↗
PubMed1998

Autosomal recessive cornea plana. A clinical and genetic study of 78 cases in Finland.

PURPOSE: To review the literature of autosomal recessive cornea plana (RCP) and to perform a clinical and genetic study on this disorder in Finland. The 78 Finnish RCP patients represent the majority of RCP cases worldwide; outside Finland only 35 cases have been reported. METHODS: Families with RCP, particularly in northern Finland, have been followed up by the senior author since the 1950s and extensive genealogical studies have been made. RESULTS: The most typical symptoms are greatly reduced corneal refraction, 25-35 dioptres, causing strong hyperopia, slight microcornea, an extended limbus zone, a central, deep corneal opacity and a marked arcus senilis, seen even before the age of 20. We present a pedigree comprising 33 affected persons with cornea plana. We have mapped the two genes for the dominantly and the recessively inherited type of cornea plana to the same region on the long arm of chromosome 12, (12q21). CONCLUSIONS: In northern Finland RCP has a higher frequency than elsewhere, probably as a result of a strong founder effect in the population that arrived in these regions approx. 400 years ago. The strong accumulation of this rare disease in these isolated areas and the strong genealogical connections between different families with RCP, suggest that probably all the Finnish RCP cases are caused by the same mutation.

Adolescent↗
PubMed1997

Autosomal dominant cornea plana: clinical findings in a Cuban family and a review of the literature.

Cornea plana may occur in connection with malformations of the eye or of other parts of the body. As an isolated ocular anomaly, it may be inherited in an autosomal recessive or in an autosomal dominant fashion. We have previously mapped genes for both forms of the disease to 12q21. We studied 36 members of three generations of a Black Cuban family with autosomal dominant cornea plana. Three affected males and 11 affected females were examined. Corneal refraction varied between 37.50 and 42.75 diopters. Horizontal corneal diameter ranged from 8.75 to 11.25 mm. The cornea was clear and the limbal zone only occasionally widened. A marked arcus senilis was present in six patients aged 30 to 58 years, but in none of their healthy relatives. The anterior chamber was shallow in those affected, varying in depth from 1.68 to 2.38 mm. One woman was blind from closed-angle glaucoma. The axial length was within normal limits in all patients.

Adolescent↗
PubMed1996

Dominantly and recessively inherited cornea plana congenita map to the same small region of chromosome 12.

Cornea plana congenita occurs in a mild autosomal dominant (CNA1) and a more severe autosomal recessive (CNA2) form. We recently assigned a CNA2 locus to a region on chromosome 12 by linkage analysis and excluded linkage to that locus in two Finnish CNA1 families. Here we describe a Cuban pedigree in which 14 members are affected with dominantly inherited cornea plana. By linkage analysis this phenotype was mapped to the immediate vicinity of markers D12S82 and D12S351 on 12q, that is, precisely the same small region (3 cM or less) to which CNA2 previously had been assigned. Our results support the existence of at least three genetically distinct forms of cornea plana. It remains to be determined whether recessive and dominant cornea plana are caused by different mutations of a single gene or whether the region in 12q harbors two or more genes whose mutations cause corneal maldevelopment.

Chromosome Mapping↗
PubMed1996

The genetics of cornea plana congenita.

Cornea plana congenita is believed to occur in a mild autosomal dominant (CNA1) and a more severe autosomal recessive (CNA2) form. We recently assigned a CNA2 locus to a region on chromosome 12 by linkage analysis. In this study we compared these traits clinically and genetically. Using the horizontal corneal refraction value in diopters (D) as a parameter, a control population (n = 473) had a mean value of 43 center dot 4 (SD 1 center dot 5 D) for men and 43 center dot 7 (SD 1 center dot 6 D) for women, whereas in 51 subjects affected with CNA2 the mean value was 29 center dot 9 (SD 5 center dot 2 D) and in five subjects affected with CNA1 the mean value was 37 center dot 8 (SD 1 center dot 6 D). By linkage analysis in two CNA1 families the CNA2 locus could be conclusively excluded. These data suggest that at least two forms of hereditary cornea plana exist which are both clinically and genetically distinct.

Adolescent↗
PubMed1995

Linkage disequilibrium mapping of the cornea plana congenita gene CNA2.

We recently assigned a gene for autosomal recessive cornea plana congenita (CNA2; MIM No. 217300) by linkage analysis to the approximately 3-cM interval between markers D12S82 and D12S327. Here, we extended these studies by exploiting the haplotype and linkage disequilibrium information that can be derived from the genetically isolated Finnish population and its subpopulations. By testing 32 independent families with 10 polymorphic markers in the CNA2 interval, strong allelic association between CNA2 and a set of markers with a peak at marker D12S351 was detected. Based on linkage disequilibrium analysis, the critical region for CNA2 could be narrowed to only 0.04-0.3 cM from marker D12S351, thus defining a critical interval 0.08-0.60 cM in length. These results provide a basis for highly focused positional cloning of CNA2.

Chromosome Aberrations↗
PubMed1995

Cornea plana congenita gene assigned to the long arm of chromosome 12 by linkage analysis.

We report the mapping of the locus for autosomal recessive cornea plana congenita (CNA2; MIM 217300) by linkage analysis to the approximately 10-cM interval between markers D12S82 and D12S327. The recessively inherited disorder studied here is more severe than dominant forms. Its main manifestations are reduced curvature and hazy limbus of the cornea, opacities in the corneal stroma, and marked corneal arcus at early age. Our results provide a starting point for the positional cloning of CNA2 and the elucidation of the pathogenesis of the disease.

Adult↗
PubMed1995

Changes of the eye caused by the climate in Rwanda, Africa.

Rwanda is a small but densely populated country, situated at the watershed between East and West Africa, close to the equator. The mean elevation is around 1500 m. We studied 114 males (mean age 28.42 years) and 111 females (mean age 29.84 years) at the ophthalmological outpatient department of the Centre Hospitalier in Kigali. Changes to the eye caused by the climate were fewer than expected. Only 10 patients (5 males, 5 females) with pterygium (mean age 33.0 years), and four males and two females with climatic droplet keratopathy (mean age 47.5 years) were observed. However, the size of the pinguecula was marked. Corneal thickness, measured with Haag-Streit's device, averaged 0.524 mm in 38 males and 0.521 mm in 38 females. The Rwandans showed a normal chamber depth, a mean of 2.98 mm being noted in 107 males and a mean of 2.80 mm in 106 females.

Adolescent↗
PubMed1993

[Not Available].

Explore the source record for details and available documents.

Finland↗
PubMed1992

Juvenile cataract with autosomal recessive inheritance. A study from the Aland Islands, Finland.

Juvenile (including congenital and infantile) cataract occurs commonly as part of a more generalized or systematic condition, or as a component of a syndrome. Isolated juvenile cataract is a relatively rare disorder and the mode of inheritance is often autosomal dominant. Autosomal recessive transmission of isolated juvenile cataract is rare. The present paper is a report of 15 cases of juvenile cataract on the Aland Islands (Finland) with about 23,000 inhabitants. Twelve belong to 7 sibships of two different pedigrees and 3 cases are sporadic, of which we have found no genealogical connections in the last 6-10 generations to the two cataracta pedigrees. One of the sporadic cases presented an operated cleft palate and a chromosomal anomaly. In another sporadic case the mother probably had been infected with rubella during early gestation. In the third sporadic case the cataract was combined with partial aniridia, but he has several genealogical connections to one of the cataract pedigrees. Consanguinity between the parents was detected in 5 of the 7 sibships, in some even on various ancestral levels. Apart from the cataracts, all patients were healthy, with normal intellect, behavior, hearing, growth and development. They were neurologically intact and there were no ocular lesions apart from cataract. In the Alandic familial cases the cataracts appear to be an autosomal recessive trait. A family branch originating from southwestern Sweden and south Norway showed transmission of the cataract in three successive generations. The possibility of quasi-dominant inheritance is discussed against the background that autosomal recessive juvenile cataract may not be so rare as the small number of recorded cases would suggest.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Clinical and electroretinographic comparison between Aland Island eye disease and a newly found related disease with X-chromosomal inheritance.

Two subjects representing AIED (Aland Island Eye Disease) and a family with 5 males affected with an AIED related X-linked hereditary eye disease were studied clinically and electrophysiologically. The clinical picture of AIED includes myopia and astigmatism, reduced visual acuity, nystagmus, ocular albinism, hemeralopia and dyschromatopsia (No. 300600, McKusick 1990). The subjects with the related disease showed astigmatism with or without myopia, reduced visual acuity, slight hemeralopia, normal color vision in 3/5 subjects, no ocular albinism and nystagmus only in one case. In both diseases the ERG was abnormal showing defective a- and b-waves, but there were also differences. The most notable was the greater reduction of the b-wave amplitude in the mixed (rod and cone) responses for the white stimulus in the ERG of the AIED related disease. With regard to the pathogenesis we propose that in both diseases rod and cone functions are defective but in an AIED related disease a defective cone function inhibits the transmission of the rod signals to the rod bipolars, causing greatly reduced mixed responses. The clinical and ERG findings of this study suggest that the 5 subjects of our family do not represent AIED but another X-linked hereditary eye disease. The investigation to find out the gene locus of this disease is going on.

Adolescent↗
PubMed1991

[Treatment of obesity in children and adolescents].

Weight development was compared in 48 obese children, 6-15 years of age, who during a 12-month period underwent treatment either individually, in groups, or as part of the school health services. Those treated intensively by groups or individually manifested a relative weight reduction of 10-14 per cent at the 12-month follow-up, as compared with seven per cent in those treated by the school health services, but at five-year follow-up relative weight reduction was much the same in all three categories. Thus, group treatment of childhood obesity would appear to be the best alternative as it yields fairly rapid relative weight reduction with beneficial metabolic changes, and entails less investment in personnel resources.

Adolescent↗
PubMed1991

Localization of the Aland Island eye disease locus to the pericentromeric region of the X chromosome by linkage analysis.

Aland Island eye disease (AIED) is an X-chromosomal disorder characterized by reduced visual acuity, progressive axial myopia, regular astigmatism, latent nystagmus, foveal hypoplasia, defective dark adaptation, and fundus hypopigmentation. The syndrome was originally reported in 1964 in a family on the Aland Islands. To determine the localization of the AIED gene, linkage studies were performed in this family. total of 37 polymorphisms, covering loci on the entire X chromosome, were used. By two-point analysis the strongest evidence for linkage was obtained between AIED and DXS255 (maximum lod score [Zmax] 4.92 at maximum recombination fraction [theta max] .00). Marker loci DXS106, DXS159, and DXS1 also showed no recombination with AIED. Other positive lod scores at theta max .00 were obtained with markers localized in the XY homologous region in Xq13-q21, but the numbers of informative meioses were small. Multilocus linkage analysis indicated that the most probable location of AIED is in the pericentromeric region between DXS7 and DXS72. These results rule out localizations of AIED more distal on Xp that have been proposed by others. Our data do not exclude the possibility that AIED and incomplete congenital stationary night blindness are caused by mutations in the same gene. This question should be resolved by careful clinical comparison of the disorders and ultimately by the molecular dissection of the genes themselves.

Albinism, Ocular↗