PubMed Health⌕ Search

Biomedical subjects

J Leisti

Publications and source records attributed to J Leisti.

At least 19 recordsLinked to original sources
PubMed1992

Unstable DNA may be responsible for the incomplete penetrance of the myotonic dystrophy phenotype.

Myotonic dystrophy (DM) is associated with the expansion and instability of a trinucleotide (CTG) repeat in a sequence encoding a cAMP-dependent protein kinase. The normal copy number of 5-35 repeats is exceeded in DM patients, with the size of the expansion broadly correlating with the severity of symptoms experienced. In most families reported, the unstable DNA sequence has increased in size on transmission to affected offspring, thereby providing a molecular explanation for the phenomenon of anticipation in DM, i.e. an increase in the severity of symptoms associated with an earlier age at onset of the disease in successive generations of a family. Here we present the first reported case of a family where the transmission of the affected chromosome from father to son is accompanied by a reduction in the size of the triplet expansion, such that it falls within the normal range. As the son remains asymptomatic, this type of molecular event may provide an explanation for the incomplete penetrance of the disease phenotype reported for this disorder. The implications for genetic counselling of DM families and the mechanistic considerations of the trinucleotide instability are discussed.

Adult↗
PubMed1992

Identification of a common mutation in Finnish patients with nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an autosomal recessive metabolic disorder caused by the defects in the glycine cleavage system (GCS; EC 2.1.2.10), a multienzyme system that consists of four individual components. NKH is a rare disorder in many countries, but with a very high incidence in northern Finland. To understand the genetic background of this high incidence, we examined the GCS in a typical case of NKH at the molecular level. The activity of P protein, a component of the GCS, was not detected in the lymphoblasts of the patient, while P protein mRNA of a normal size and level was present in the cells. Structural analysis of P protein mRNA from the patient revealed a single nucleotide substitution from G to T in the protein coding region, which resulted in an amino acid alteration from Ser564 to Ile564. No P protein activity was detected when the mutant P protein with this amino acid substitution was expressed in COS 7 cells. The patient was homozygous for this mutation. Furthermore, this mutation was present in 70% (14 of 20) of P protein gene alleles in Finnish patients with NKH, whereas it was not found in 20 alleles of non-Finnish patients. The results suggest that this mutation is responsible for the high incidence of NKH in Finland.

Amino Acid Metabolism, Inborn Errors↗
PubMed1992

Fumarase deficiency: two siblings with enlarged cerebral ventricles and polyhydramnios in utero.

A family having two boys with progressive encephalomyopathy and fumaric aciduria due to fumarase deficiency is described. Both patients initially presented with polyhydramnios and enlarged cerebral ventricles in utero, with subsequent cerebral atrophy, severe developmental delay, infantile spasms, and hypsarythmia on electroencephalogram. Fumarase activity in blood mononuclear cells and in the mitochondrial and cytosolic fractions of cultured skin fibroblasts was less than 0.5% of the control mean or undetectable. The older boy died at the age of 5 years and 4 months and the younger one is now 2 years and 10 months. The unrelated parents are symptomless and the other three children in the family are clinically healthy. Fumarase activities in the blood mononuclear cells of the father, mother, sister, and two brothers were 59%, 52%, 52%, 120%, and 44% of the control mean, respectively. The results strongly support autosomal recessive inheritance of fumarase deficiency and suggest its consideration in children with congenital hydrocephalus, progressive brain atrophy, and infantile spasms.

Cells, Cultured↗
PubMed1991

Uridine enhances expression of the fragile X chromosome in human lymphocytes.

We have studied the effect of uridine on the expression of fragile X (fra[X]) in lymphocyte cultures established in the folate and thymidine deficient medium TC199. The results indicate that uridine enhances the expression of fra(X) and gives a higher mitotic rate. The excess of uridine during DNA synthesis might further promote the previously suggested cycle of misincorporation and removal of deoxyuridine monophosphate when the pool of deoxythymidine triphosphate is continuously depleted.

Culture Media↗
PubMed1990

Linkage disequilibrium detected between dystrophia myotonica and APOC2 locus in the Finnish population.

Three polymorphic loci APOC2, CKMM and p134C were used to haplotype 15 Finnish dystrophia myotonica (DM) families representing about one third of all DM patients in this isolated population. Compound APOC2 and CKMM haplotypes reveal linkage disequilibrium: 90% of DM chromosomes co-occur with the haplotypes that occur in 31% of normal chromosomes only. The same disequilibrium is present when only polymorphisms occurring at the APOC2 locus are used. Surprisingly, no statistically significant linkage disequilibrium was discovered at the CKMM locus alone. Of the meiotic events, 84% were informative when both APO2 and CKMM loci were used. When studied selectively, 60% of meiotic events were informative at the APOC2 locus, whereas CKMM alone resulted in 65% meiotic informativeness. The distal marker p134C was found to have an unfortunately low information content in our population.

Alleles↗
PubMed1990

Prenatal diagnosis of single gene disorders in northern Finland.

Prenatal diagnosis of single gene disorders is challenging because of the multidisciplinary diagnostic approach and the genetic counselling needed. Out of 3100 pregnancies of northern Finnish women studied for early detection of congenital defects or genetic disease, 110 were at risk for and 15 were unexpectedly found to carry a fetus with a single gene disorder. Seven of the 21 diseases studied were typically representative of inherited diseases in northern Finland. The diagnostic approaches used included fetal ultrasonography, analysis of the components of the amniotic fluid, fetal enzyme analysis, fetal karyotyping for the fragile X syndrome, and fetal DNA analysis. Altogether, 50 pregnancies were found to be affected; 11 of these were continued because the diagnosis was too late for termination, and seven because the parents wanted it. Prenatal diagnosis of severe hereditary disease can be enhanced by improving the detection of pregnancies at risk, and by developing methods for earlier fetal diagnosis.

Adult↗
PubMed1989

Muscle-eye-brain disease (MEB)

Clinical features of a rare congenital myopathy, muscle-eye-brain (MEB) disease, are described in 19 patients. The pedigree data suggest an autosomal recessive inheritance. The patients presented with congenital hypotonia and muscle weakness. Serum CK was elevated, EMG was myopathic and muscle biopsy showed slight or moderate changes compatible with muscular dystrophy. Ophthalmological findings included severe visual failure and uncontrolled eye movements associated with severe myopia. The flash VEPs were exceptionally high, whereas non-corneal ERG was unrecordable. The EEG showed progressive abnormalities after the age of 6 months. Psychomotor development was slow during the first years of life, and mental retardation was severe. Most patients began to deteriorate around age 5 years. This change included spasticity and joint contractures. CT scans showed ventricular dilatations and abnormally low white matter density in several patients. Spasticity, high VEPs and ocular manifestations differentiate MEB from the Fukuyama type congenital muscular dystrophy.

Adolescent↗
PubMed1988

Familial occurrence of malignant lymphoepithelial lesion of the parotid gland in a Finnish family with dominantly inherited trichoepithelioma.

A rare malignant lymphoepithelial lesion (MLEL) of the parotid gland is described in a mother and daughter within one Finnish family. Several cases of dominantly inherited trichoepithelioma were observed in the same family. This is the third published case of familial MLEL, and the first in whites. The simultaneous occurrence of MLEL with hereditary trichoepithelioma is a new finding and may suggest a common genetic background and/or etiology.

Female↗
PubMed1988

A syndrome of multiple congenital contractures: neuropathological analysis on five fetal cases.

We performed a neuropathological study on 5 fetuses with an autosomal recessive, lethal syndrome of congenital contractures diagnosed by fetal hydrops on ultrasonography. The fetuses showed a typical pattern of malpositioning of hips and knees with occasional pterygia of the neck and elbows. The muscles were hypoplastic and the spinal cords showed severe thinning, most markedly affecting the ventral half. A total loss of axons in the ventral and lateral funiculi, subtotal loss of anterior horn motor neurons with accompanying astrocytosis and astrogliosis, and similar but less severe changes at the brain stem level suggested a degenerative rather than a dysmorphogenetic mechanism. Sensory nuclei and pathways were distinctly less severely affected, if at all. The findings further delineate this condition as a genetically and pathoanatomically distinct autosomal recessive syndrome.

Abnormalities, Multiple↗
PubMed1987

Early prenatal diagnosis of a lethal syndrome of multiple congenital contractures.

An ultrasonic diagnosis of a lethal, autosomally recessive syndrome of multiple congenital contractures was made in seven high-risk pregnancies on the 13rd to 17th gestational weeks. The diagnostic findings were the development of progressive subcutaneous oedema from the 13th gestational week on and the decrease of fetal limb movements.

Abnormalities, Multiple↗
PubMed1985

The incidence of Down syndrome in northern Finland with special reference to maternal age.

The incidence of live-born children with Down syndrome was found to be 1.73/1000 (1:578) in northern Finland over the years 1965 to 1979. Despite a marked reduction in the proportion of older mothers, no significant change in the incidence was observed. Instead, an age-specific rise in the incidence for mothers aged 25 to 29 years could be shown during the last five-year period in years 1975 to 1979.

Adult↗
PubMed1979

Wegener's granulomatosis in childhood. A clinical report based on 3 cases.

Wegener's granulomatosis is a very rare disease in children; only 10 cases have been reported in the literature. The present report describes 3 cases where Wegener's granulomatosis developed at an early stage, beginning with upper respiratory tract symptoms. All the 3 children have been successfully treated with a combination of azathioprine and corticosteroids.

Adolescent↗