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H Boman

Publications and source records attributed to H Boman.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mutations in the iduronate-2-sulfatase gene in five Norwegians with Hunter syndrome.

We have identified the mutations in the iduronate-2-sulfatase (IDS) gene of five unrelated Norwegians with Hunter syndrome by reverse transcription-polymerase chain reaction (RT-PCR) analysis of IDS mRNA followed by single strand conformation polymorphism (SSCP) analysis and cDNA sequencing. One patient had a 5-bp deletion, located at the intron 5/exon 6 junction, that created a new alternative splice site. This expanded the deletion to 9 bp in mRNA, an in-frame deletion of the first 3 codons of exon 6 of the IDS gene. In two patients point mutations were identified, the S333L mutation, which has been reported previously, and A346D (a C-->A transversion at nucleotide 1161/exon 8), which is novel. Two patients had large 3' mRNA rearrangements. The A346D mutation was associated with the mild phenotype, all others with the severe form.

Adolescent↗
PubMed1996

The Ca(2+)-sensing receptor gene (PCAR1) mutation T151M in isolated autosomal dominant hypoparathyroidism.

Isolated autosomal dominant hypoparathyroidism is a heterogeneous disorder characterized by parathyroid hormone (PTH) deficiency, hypocalcemia and hyperphosphatemia. The candidate gene approach was used to study a large Norwegian family. The loci for the PTH gene, PTH receptor gene and RET protooncogene were excluded using dinucleotide markers and restriction fragment length polymorphism analysis. Complete cosegregation of this trait was found with the chromosomal region 3q13, using the short tandem repeat markers D3S1267, D3S1269, D3S1303, D3S1518, and RHO. This region contains the candidate locus for the Ca(2+)-sensing receptor (PCAR1). By single-strand conformation polymorphism (SSCP) analysis of all PCAR1 exons followed by automated sequencing, we identified a C to T transition in exon 2 (cDNA position 452) on the mutant allele in the family. The mutation predicts a substitution of Thr to Met in amino acid position 151 (T151M). A StyI restriction site created by the nucleotide substitution was used to confirm the mutation on all alleles, as well as to exclude it among 100 normal alleles (blood donors). SSCP analysis also identified a novel polymorphism of PCAR1 intron 4 (1609-88t --> c) on normal alleles. The T151M mutation is located in the extracellular N-terminal domain of PCAR1, which belongs to the superfamily of G protein-coupled receptors. We suggest that this is a gain-of-function mutation that increases the sensitivity of the receptor to [Ca2+], thereby decreasing the calcium set point.

Amino Acid Sequence↗
PubMed1996

Relative frequency, heterogeneity and geographic clustering of PKU mutations in Norway.

We have analysed 236 Norwegian phenylketonuria (PKU) alleles by a combination of mutation scanning methods, restriction enzyme-based assays and DNA sequencing. Thirty-three different mutations constituted 99.6% of all mutant alleles (only 1 allele remains unidentified), 23 of these have been identified also in other European countries. Twenty were predicted missense mutations, 6 splice mutations, 4 nonsense mutations and 2 deletion mutations and 1 mutation disrupted the start codon. The 8 most common mutations represented 83.5% of the PKU alleles, with single allele frequencies ranging from 5.9 to 15.7%. Four of these mutations (R261Q, R408W, Y414C, and 1VS12nt1) are commonly occurring also in PKU patients in other European countries, while the other 4 (G46S, G272X, F299C, and R408Q) have higher frequencies in Norway than in any other country studied. Six mutations (I65T, L249F, P281L, Y356X, R158Q, and R252W) have frequencies between 0.8% and 2.1%, and 19 mutations were encountered only once. The majority of PKU mutations were found on the same RFLP/VNTR haplotype backgrounds in Norway as in other European populations, suggesting that only a few of the mutations may represent recurrent mutations (< 3.4%). Among 10 mutations only reported for our population, we detected 2 de novo mutations (0.8%) arisen in Norway. From the birthplaces of the probands' grandparents, each mutation seemed to have an individual geographic distribution within Norway, with patterns of local mutation clustering. Our observations are compatible with multiple founder effects and genetic drift for the distribution of PKU mutations within Norway.

Alleles↗
PubMed1994

[Indirect genetic diagnosis of cystic fibrosis].

The diagnosis cystic fibrosis was made in a three years old girl. Her older brother and her mother's sister both had minor symptoms and signs suggestive of this disease. None of 17 mutations in the gene locus for cystic fibrosis was identified in the patient by DNA-analyses. By haplotype analyses her brother, but not her aunt, was shown to share the proband's haplotypes. This family is used as an example of the general diagnostic potential of indirect diagnosis of genetic disease by haplotype analysis. The prerequisite for haplotype analysis is the availability of DNA from both the patient and the patient's relatives, stressing the need for a DNA bank of material from persons with inherited disorders, for future use.

Child, Preschool↗
PubMed1993

[Analysis of the Duchenne muscular dystrophy gene with PCR analysis in paraffin-embedded tissue. A new diagnostic possibility].

Analysis of DNA from archival, paraffin-embedded muscle tissue allowed tracing of the mutated dystrophin gene in two families with Duchenne muscular dystrophy. There were no living patients in these families. In one family this diagnosis contributed to the birth of a normal male, in the other family to the demonstration of carrier status. These analyses, based on the polymerase chain reaction, are relatively rapid and simple, and lend increased value to old tissue samples stored in pathology departments.

DNA↗
PubMed1993

[DNA diagnosis of fragile X syndrome in a family. A new type of heredity--dynamic mutations].

In typical cases, the diagnosis of fragile X syndrome can be made clinically, but has so far been based on cytogenetic detection of a fragile site on the X chromosome at Xq27.3. Cytogenetic analyses are time-consuming, and false negative results have been a problem. Following the successful molecular cloning of the gene causing the fragile X syndrome, a novel genetic principle was discovered: the "dynamic" DNA mutation. DNA analyses have now the power to distinguish between normal copies of the gene, carrier mutations and fragile X mutations. We have performed both cytogenetic and DNA analyses in an extended fragile X family. DNA fragment length variations in the gene were identified by Southern blot analysis, and the results were used diagnostically in the family. Instability of the mutation (dynamic mutation) occurred between generations and within individuals. DNA analysis, as performed here, improves diagnostic accuracy and genetic counselling in fragile X families.

Blotting, Southern↗
PubMed1992

A de novo phenylketonuria mutation: ATG (Met) to ATA (Ile) in the start codon of the phenylalanine hydroxylase gene.

We here describe the detection of a de novo mutation in the phenylalanine hydroxylase gene in a Norwegian phenylketonuria (PKU) patient. This novel mutation, M1I, disrupts the start codon of the gene by a G to A transition. The compound heterozygote genotype (IVS-12/M1I) of this patient predicts that no phenylalanine hydroxylase enzyme is formed, thus leading to a severe classical PKU. Determination of haplotypes and DNA fingerprint patterns indicates a paternal origin of the de novo mutation.

Adult↗
PubMed1992

PKU mutations R408Q and F299C in Norway: haplotype associations, geographic distributions and phenotype characteristics.

Details are given concerning the phenylketonuria (PKU) mutations R408Q and F299C. Both mutations were identified among 47 PKU patients, derived from the Norwegian PKU registry. A novel PKU mutation (R408Q) was identified, by single-strand conformation polymorphism analysis, on six out of eight mutant haplotype 12 chromosomes and on none of the other PKU chromosomes. The F299C mutation occurred exclusively on mutant haplotype 8, and was the only mutation associated with this haplotype (on six chromosomes). One patient homozygous for each mutation was found. The patient homozygous for F299C manifested severe PKU, whereas the R408Q homozygote exhibited a mild PKU variant. Pedigree analysis of these families has not, so far, revealed consanguinity. Information on the place of birth of the relevant grandparents of the PKU patients with these mutations suggests that each of these mutations in Norway has originated from a common gene source.

Adolescent↗
PubMed1992

Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21.

We studied the mechanism of ring chromosome 21 (r(21)) formation in 13 patients (11 unique r(21)s), consisting of 7 from five families with familial r(21) and 6 with de novo r(21). The copy number of chromosome 21 sequences in the rings of these patients was determined by quantitative dosage analyses for 13 loci on 21q. Nine of 11 r(21)s, including the 5 familial r(21)s, showed no evidence for duplication of 21q sequences but did show molecular evidence of partial deletion of 21q. These data were consistent with the breakage and reunion of short- and long-arm regions to form the r(21), resulting in deletion of varying amounts of 21q22.1 to 21qter. The data from one individual who had a Down syndrome phenotype were consistent with asymmetric breakage and reunion of 21q sequences from an intermediate isochromosome or Robertsonian translocation chromosome as reported by Wong et al. Another patient, who also exhibited Down syndrome, showed evidence of a third mechanism of ring formation. The likely initial event was breakage and reunion of the short and long arms, resulting in a small r(21), followed by a sister-chromatid exchange resulting in a double-sized and symmetrically dicentric r(21). The phenotype of patients correlated well with the extent of deletion or duplication of chromosome 21 sequences. These data demonstrate three mechanisms of r(21) formation and show that the phenotype of r(21) patients varies with the extent of chromosome 21 monosomy or trisomy.

Alleles↗
PubMed1992

Lack of transmission of deleted mtDNA from a woman with Kearns-Sayre syndrome to her child.

We have investigated the daughter of a woman with Kearns-Sayre syndrome. The woman had a high percentage of deleted mtDNA in muscle, but no deleted mtDNA was detected in fibroblasts, bone marrow, and peripheral blood cells by Southern blot analysis. With PCR, analytical sensitivity was significantly increased, and deleted mtDNA was detected in all examined tissues from this patient. The patient had healthy parents and nine healthy siblings. No deleted mtDNA was detected in blood from the mother of the patient. The patient had an uneventful pregnancy and delivered at term. Deleted mtDNA could not be detected in placenta by Southern blot analysis. With PCR, deleted mtDNA was detected in the majority of placental specimens. This finding may, however, be due to contamination with maternal DNA. The patient's daughter was healthy at age 5 mo, and morphologic examination of muscle was normal. No transmission of deleted mtDNA to the daughter could be detected by Southern blot and PCR analysis of peripheral blood cells, bone marrow, fibroblasts, and muscle. The presence of deleted mtDNA was excluded at a fractional level of less than 1:100,000 in all examined tissues from the daughter.

Adolescent↗
PubMed1991

Application of natural and amplification created restriction sites for the diagnosis of PKU mutations.

PCR amplification, either conventional, or as site directed mutagenesis using primers with mismatched 3'-ends, followed by restriction endonuclease digestion, provides rapid, non-isotope assays of known mutations in the human phenylalanine hydroxylase gene. Such assays were shown to have the potential to detect all of the 18 presently reported phenylketonuria mutations. The practical applicability of this approach was demonstrated for eight mutations in Norwegian phenylketonuria patients, among them the most common ones.

Base Sequence↗
PubMed1990

A termination mutant prevalent in Norwegian haplotype 7 phenylketonuria genes.

RFLPs in the phenylalanine hydroxylase (PAH) gene locus were determined in 47 Norwegian nuclear families that had at least one child with phenylketonuria (PKU). The PKU haplotype distribution differed somewhat from that of other European populations. Mutant haplotype 7 is relatively rare in other populations but constituted 20% of all mutant haplotypes in Norway. In 14 of the 17 mutant haplotypes 7, a previously unreported deletion of the BamHI restriction site in exon 7 of the PAH gene was observed. The abrogation of the BamHI site was shown to be due to a G-to-T transversion, changing Gly 272 to Ter 272 in exon 7 of the gene, thus directly identifying the PKU mutation. Unlike the families of the other PKU patients, the families with this mutation clustered along the southeastern coast of Norway, suggesting a founder effect for this mutation.

Adolescent↗