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Biomedical subjects

U Kristoffersson

Publications and source records attributed to U Kristoffersson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Autosomal dominant primary hyperparathyroidism and jaw tumor syndrome associated with renal hamartomas and cystic kidney disease: linkage to 1q21-q32 and loss of the wild type allele in renal hamartomas.

Hereditary hyperparathyroidism-jaw tumor syndrome (HPT-JT) is an autosomal dominant disease (OMIM 145001) that has recently been mapped to chromosomal region 1q21-q32 (HRPT2). Here we report two families with HPT-JT syndrome in which adult renal hamartomas or cystic kidney disease were prominent associated features, possibly representing a new phenotypic variant of the HPT-JT syndrome. In the first family, renal lesions were present in five out of six affected individuals, whereas HPT and JT were seen in four and two cases, respectively. In the second family, JT was found in three of the five affected individuals and two affected members also exhibited polycystic kidney disease. The possibility of the latter cosegregating as a separate autosomal dominant gene can not be ruled out. A sex-dependent penetrance of primary HPT, resulting in predominantly male-affected cases was evident in the two families. Twenty microsatellite markers in the HRPT2 region were typed, in addition to markers in the multiple endocrine neoplasia (MEN) types 1 and 2 regions at 11q13 and 10q11. The disease in these two kindreds was linked to five markers in the 1q21-q32 region (logarithm-of-odds scores: 3.2-4.2), whereas linkage to the MEN1 and MEN2 regions was excluded. Meiotic recombinations detected in affected individuals placed the locus telomeric of D1S215, thus narrowing the HRPT2 region from > 60 to approximately 34 centimorgans. Loss of heterozygosity was studied in seven renal hamartomas from two affected individuals in the first family, as well as in a jaw tumor and a parathyroid tumor from the second family. All renal hamartomas showed loss of heterozygosity at the 1q21-q32 region. The losses invariably involved the wild type allele derived from the unaffected parent, suggesting the inactivation of a tumor suppressor gene in this region.

Adult↗
PubMed1995

Fifty probands with extra structurally abnormal chromosomes characterized by fluorescence in situ hybridization.

Extra structurally abnormal chromosomes (ESACs) are small supernumerary chromosomes often associated with developmental abnormalities and malformations. We present 50 probands with ESACs characterized by fluorescence in situ hybridization using centromere-specific probes and chromosome-specific libraries. ESAC-specific libraries were constructed by flow sorting and subsequent amplification by DOP-PCR. Using such ESAC-specific libraries we were able to outline the chromosome regions involved. Twenty-three of the 50 ESACs were inverted duplications of chromosome 15 [inv dup(15)], including patients with normal phenotypes and others with similar clinical symptoms. These 2 groups differed in size and shape of the inv dup(15). Patients with a large inv dup(15), which included the Prader-Willi region, had a high risk of abnormality, whereas patients with a small inv dup(15), not including the Prader-Willi region, were normal. ESACs derived from chromosomes 13 or 21 appeared to have a low risk of abnormality, while one out of 3 patients with an ESAC derived from chromosome 14 had discrete symptoms. One out of 3 patients with an ESAC derived from chromosome 22 had severe anomalies, corresponding to some of the manifestations of the cat eye syndrome. Small extra ring chromosomes of autosomal origin and ESACs identified as i(12p) or i(18p) were all associated with a high risk of abnormality.

Abnormalities, Multiple↗
PubMed1995

Characterization of add(1)(p36) in non-Hodgkin lymphomas by fluorescence in situ hybridization.

Chromosome rearrangements involving chromosome I, band p36, are among the most common aberrations in non-Hodgkin lymphomas (NHL). We have studied nine cases of NHL with add(1)(p36) using fluorescence in situ hybridization (FISH) from a series of 205 cases. Five were follicular low-grade NHL and four were follicular or diffuse high-grade NHL. Three of the five cases with follicular low-grade NHL did not contain the 14;18 translocation. The extra material on the add(1)(p36) in these three cases was derived from chromosome segment 2q31-qter; in one it was observed as a sole clonal rearrangement. In the two remaining cases, with t(14;18), the add(1)(p36) consisted of material from chromosome arms 3q and 17q, respectively. In the four cases of high-grade NHL, the material added on to Ip36 was derived from chromosomes 6, 9, 17, and 19, respectively. Using a Ip36-specific probe, DIS94, we showed a deletion on the add(1) in one of the cases with low-grade NHL, whereas no loss was observed in one of the cases with high-grade NHL. Our study indicates that cytogenetically similar add(1)(p36) are found in both high- and low-grade NHL, and the breakpoint on Ip36 as well as the origin of translocated material may vary.

Blotting, Southern↗
PubMed1995

Clinical and immunohistochemical findings in a case of neonatal Marfan syndrome.

A newborn girl with extreme cardiomegaly discovered by fetal ultrasound after 34 gestational weeks is presented. The girl was delivered through a Caesarean section. After birth, multiple skeletal stigmata and generalized cardiac involvement with abnormal valves and dilated great arteries suggested Marfan syndrome. The girl died at the age of 10 h. The postmortem examinations showed cardiovascular lesions typical of Marfan syndrome. Immunofluorescence studies from cultured fibroblasts of the patient showed decreased amounts of immunostained fibrous material, supporting the clinical diagnosis of a severe Marfan syndrome.

Antibodies, Monoclonal↗
PubMed1994

Swedish survey on extra structurally abnormal chromosomes in 39 105 consecutive prenatal diagnoses: prevalence and characterization by fluorescence in situ hybridization.

During 7 years (1985-1992), 39,105 consecutive prenatal diagnoses (34,908 amniocenteses and 4197 chorionic villus samples) were made at the five largest clinical genetic laboratories in Sweden. Thirty-one cases of extra structurally abnormal chromosomes (ESACs) were found, giving a total prevalence of 0.8 per 1000. Twelve ESACs were inherited, 14 were de novo and in five the parental origin was unknown. This gives an estimated prevalence of 0.3-0.4 per 1000 for familial and 0.4-0.5 per 1000 for de novo ESACs. Retrospectively, the ESACs were characterized by fluorescence in situ hybridization (FISH). In nine cases, no material was available for this analysis. In 21 of the remaining 22 cases, the chromosomal origin could be identified by FISH. Seventeen of these (81 per cent) were derived from the acrocentric chromosomes, of which 13 originated from chromosome 15 (62 per cent). The most common ESAC was the inv dup(15) (57 per cent). Two cases were derived from chromosome 22, one from chromosome 14, and one from either chromosome 13 or chromosome 21. The four remaining cases consisted to two i(18p)s and two small ring chromosomes derived from chromosomes 4 and 19, respectively.

Amniocentesis↗
PubMed1994

Identification, characterisation and clinical applications of cosmids from the telomeric and centromeric regions of the long arm of chromosome 22.

Using human telomeric repeats and centromeric alpha repeats, we have identified adjacent single copy cosmid clones from human chromosome 22 cosmid libraries. These single copy cosmids were mapped to chromosome 22 by fluorescence in situ hybridisation (FISH). Based on these cosmids, we established contigs that included part of the telomeric and subtelomeric regions, and part of the centromeric and pericentromeric regions of the long arm of human chromosome 22. Each of the two cosmid contigs consisted of five consecutive steps and spanned approximately 100-150 kb at both extreme ends of 22q. Moreover, highly informative polymorphic markers were identified in the telomeric region. Our results suggest that the telomere specific repeat (TTAGGG)n encompasses a region that is larger than 40 kb. The cosmid contigs and restriction fragment length polymorphism markers described here are useful tools for physical and genetic mapping of chromosome 22, and constitute the basis of further studies of the structure of the subtelomeric and pericentromeric regions of 22q. We also demonstrate the use of these clones in clinical diagnosis of different chromosome 22 aberrations by FISH.

Base Sequence↗
PubMed1993

Population-based cohort investigations of the risk for malignant tumors in first-degree relatives and wives of men with breast cancer.

BACKGROUND: Retrospective studies of familial cancer risks could be subjected to bias and should be supplemented with prospective studies if possible. Few such studies exist, and no prospective population-based study has addressed the risk for malignant tumors among relatives or wives of men with breast cancer. METHODS: All first-degree relatives and wives of 153 men whose conditions were diagnosed as male breast cancer from 1965 to 1989 in the southern health-care region of Sweden were identified through parish data. Relatives and wives alive January 1, 1958, were included in two cohorts. Their vital status and cancer morbidity were studied in the Swedish Cancer Registry, Cause of Death Registry, and Census Registry. RESULTS: The incidence for malignant tumors was significantly increased among female first-degree relatives (standardized morbidity ratio [SMR], 1.36). Significantly elevated SMR were seen for breast carcinoma (SMR, 1.80), ovarian carcinoma (SMR, 2.27), and cancer of the parotid gland (SMR, 5.58). Elevated nonsignificant SMR were seen for cancer of the cervix uteri and for bone and soft tissue sarcoma. An almost significant decreased overall cancer incidence was seen for male first-degree relatives (SMR, 0.75). The most pronounced decrease was seen for cancer of the prostate. The increased breast cancer incidence in female relatives were present in mothers, sisters, and daughters. The overall tumor incidence was not increased (SMR, 0.98) in wives of men with breast cancer. There was no significant increase in breast cancer incidence (SMR, 0.97). CONCLUSIONS: Female first-degree relatives of men with breast cancer have an elevated incidence of breast cancer and other female genital tumors, whereas male first-degree relatives have a reduced cancer incidence. Wives of men with breast cancer have a similar cancer incidence as the general population.

Bone Neoplasms↗
PubMed1993

Piebaldism in a mentally retarded girl with rare deletion of the long arm of chromosome 4.

A 4-year-old mentally retarded girl had congenital depigmentations of ventrolateral parts of the chest, abdomen, and legs. She also showed dysmorphic features of the head, thorax, and extremities, a pigmented ring in both irises, and a hernia of the left obliquus muscle. Cytogenetic investigations revealed deletion of chromosome 4 for the long arm segment q12-q21. The typical depigmentations, reported in four other patients with a similar chromosomal deletion, correspond with those in the autosomal dominant piebald trait. Mutations in the Kit protooncogene (mapped to the chromosome (4q11-4q12 region) have been found in patients affected with this dominant disorder. Piebaldism in children with developmental delay and dysmorphic features should alert the physician to the possibility of a deletion of the long arm of chromosome 4.

Abnormalities, Multiple↗
PubMed1993

Clinical impact of breakpoint position within M-bcr in chronic myeloid leukemia.

We have analyzed the M-bcr breakpoint position in 133 Philadelphia-positive chronic myeloid leukemia patients and correlated the findings with clinical, hematologic, and cytogenetic data. We also investigated the splicing pattern of the BCR-ABL mRNA in 30 patients, using reverse transcriptase PCR. No statistically significant differences were found between breakpoint position within M-bcr and clinical parameters at diagnosis, the karyotypic evolution pattern, or the leukemic phenotype during blast crisis. Furthermore, the breakpoint position within M-bcr did not correlate with the duration of chronic phase or survival time. When the splicing pattern of the BCR-ABL mRNA was compared with the results of the genomic breakpoint mapping, it was found that approximately 60% (8/14) of the patients with a 5' break expressed b2a2 fusion mRNA, whereas all patients (10/10) with a 3' break expressed b3a2 BCR-ABL mRNA.

Adolescent↗
PubMed1992

Mutation analysis and prenatal diagnosis in a Lesch-Nyhan family showing non-random X-inactivation interfering with carrier detection tests.

A nonsense mutation at the CpG-site in the codon for Arg(169) in the gene for hypoxanthine phosphoribosyltransferase (hprt) was identified by genomic polymerase chain reaction (PCR) and DNA sequencing in cultured fibroblasts from two brothers with Lesch Nyhan's syndrome. The recurrence of mutation at this CpG-site in several unrelated Lesch-Nyhan families suggests that deamination of 5-methylcytosine is a possible mechanism for mutagenesis. The level of hprt-mRNA in the fibroblasts of the patients was similar to that in healthy controls, whereas hprt-enzyme activity was not detectable. The mutation in this family was also identified in five female relatives and prenatally in a male fetus. Unexpectedly, results from hair follicle analyses and fibroblast selection studies in 8-azaguanine and 6-thioguanine medium showed a non-carrier phenotype in three of the female heterozygotes, whereas X-inactivation mosaicism was demonstrated in one heterozygote. A possible explanation for the apparent non-random X-inactivation in this family is the co-existence of the hprt mutation with an undefined X-linked lethal mutation. This observation is of practical relevance for carrier detection in other Lesch-Nyhan families.

Base Sequence↗
PubMed1992

Pseudohypoparathyroidism type I and Albright's hereditary osteodystrophy with a proximal 15q chromosomal deletion in mother and daughter.

A 33-year-old woman and her 71-year-old mother were both found to have pseudohypoparathyroidism type I with Albright's hereditary osteodystrophy associated with a cytogenetic deletion of the proximal part of one chromosome 15, resembling that found in Prader-Willi syndrome. As there are overlapping clinical features between these two syndromes a causal relationship cannot be excluded. However, molecular analyses with 10 probes from this region did not detect any uniparental disomy or deletion, features frequently found in Prader-Willi syndrome.

Adult↗
PubMed1991

Trisomy 13 as a primary chromosome aberration in acute leukemia.

Four patients with acute leukemia displayed trisomy 13 as the primary chromosome abnormality. The two patients with acute nonlymphocytic leukemia FAB-type M1 (ANLL-M1) had the karyotypes 47,XY,+13/48,XY,+13,+13 and 47,XX,+13, a patient with the hypogranular form of ANLL M3 had 47,XX,+13, and the fourth patient, who had acute undifferentiated leukemia (AUL), had the karyotype 47,XY,+13/48,XY,+8,+13. Including these four cases, a total of 24 hematologic neoplasms with an extra chromosome 13 as the sole aberration have now been reported. Except for the AUL, all have been of myeloid origin--20 ANLL, one myelodysplastic syndrome, and two chronic myeloproliferative disorders. Trisomy 13 as the sole acquired karyotypic abnormality therefore seems to be strongly associated with myeloid differentiation of the neoplastic cells and with a differentiation block leading to acute leukemia.

Acute Disease↗
PubMed1991

Increased frequency of chromosome aberrations in long-term cultured cerebrospinal fluid lymphocytes of patients with multiple sclerosis.

A method employing long-term lymphocyte culturing was developed to study chromosome aberrations in samples with very few cells. It was used to examine lymphocytes from the cerebrospinal fluid (CSF) and peripheral blood (PB) in 23 patients with clinically definite multiple sclerosis (MS), nine patients with other neurological diseases (OND), and eight healthy individuals. MS patients had significantly more aberrations in CSF lymphocytes than in PB lymphocytes (6.4 vs 4.1; P = 0.003). In contrast, no such difference was noted among patients with OND (3.8 vs. 3.7; P = 0.89) or healthy controls (3.6 vs 3.5; P = 0.90). CSF lymphocytes from MS patients had more aberrations than CSF lymphocytes from healthy controls (P = 0.012), but there was no difference between PB lymphocytes from MS patients and controls (P = 0.58). The patients with OND were similar to healthy controls both in CSF (3.8 vs 3.6; P = 0.91) and PB lymphocytes (3.7 vs 3.5; P = 0.90).

Adult↗
PubMed1991

Constitutive heterochromatin C-band polymorphism in prostatic cancer.

The size of the heterochromatin C-bands on chromosomes has been reported to be associated with some, but by no means all, human malignancies. No studies along these lines have been performed in prostatic cancer. We therefore investigated the size, incidence of inversions, and symmetry versus asymmetry of C-band heteromorphisms on chromosomes 1, 9, and 16 in peripheral blood lymphocytes from 52 prostatic cancer patients and 183 healthy individuals. There were no differences in C-band heteromorphism on chromosomes 1, 9, and 16 between the patients and the controls. Neither were there any differences when patients with early-stage disease were compared with patients with more advanced cancer. Younger (aged less than 70 years) cancer patients had significantly higher frequencies of larger C-bands on chromosomes 1 (p less than 0.01) and 16 (p less than 0.001) than did patients aged more than 70 years at diagnosis. This could indicate a possible relationship between the amount of constitutive heterochromatin on chromosomes 1 and 16 and susceptibility to early development of prostatic cancer but could also result from the age differences between the two patient groups.

Aged↗
PubMed1991

Cytogenetics of secondary myelodysplasia (sMDS) and acute nonlymphocytic leukemia (sANLL).

76 cases of secondary myelodysplasia (sMDS) and acute non-lymphocytic leukemia (sANLL) were cytogenetically analyzed. Among the 36 sMDS patients, 13 (36%) had only normal karyotypes whereas 23 (64%) displayed clonal chromosomal abnormalities. The most common aberrations were -7, 5q-, -5, and +8. In 10 patients (43% of the cytogenetically aberrant cases), clones with only one anomaly, mostly 5q- or -7, were found. Of the 40 sANLL patients, normal karyotypes were detected in 10 (25%). Among the 30 (75%) abnormal cases, the most frequent aberrations were -7, -5, +8, 7q-, -17, and +21. 12 patients (40%) had clones with single abnormalities, most often -7. In 4 sANLL patients cytogenetically unrelated clones were detected. A survey of all previously published secondary hematologic neoplasias reveals that the most frequent abnormalities in sMDS are -7 (41%), 5q- (28%), and -5 (11%), followed by der(21q), +8, 7q-, der(12p), t(1;7), -12, -17, der(17p), der(3p), der(6p), and -18. Clones with single aberrations have been found in 45% of the cases and cytogenetically unrelated clones have been described in 6%. The most common abnormalities in sANLL are -7 (38%), 5q- (17%), -5 (15%), +8 (13%), and -17 (11%), followed by der(3q), der(11q), der(12p), -21, 7q-, -18, der(3p), der(17p), +21, der(21q), der(6p), and -16. 38% of the sANLL patients have had clones with only one aberration and 3% have had unrelated clones. The frequencies of these nonrandom abnormalities in sMDS and sANLL are thus remarkably similar - the only exception appears to be 5q-, which is more common in sMDS. Also the mean number of abnormalities per case is similar - 5.3 in sMDS and 5.6 in sANLL. When the incidences of characteristic cytogenetic abnormalities were correlated with the type of previous therapy, -7 was found to be more frequent in sMDS and sANLL patients who had been exposed to chemotherapy whereas 5q- was associated with previous exposure to ionizing radiation in sMDS patients.

Aged↗
PubMed1991

Karyotypic patterns in chronic myeloproliferative disorders: report on 74 cases and review of the literature.

During the 15 year period 1975-1989, 74 cases of chronic myeloproliferative disorder (CMPD) were cytogenetically analyzed in our department. Thirty patients had polycythemia vera (PV), 23 had idiopathic myelofibrosis (MFS), 15 had idiopathic thrombocythemia (IT), and six had unclassifiable CMPD (UCMPD). The overall frequency of clonal chromosome aberrations was 36% (50% in PV, 30% in MFS, 27% in IT, and 17% in UCMPD). The frequency was markedly higher (53%) in the subset of patients who had received myelosuppressive therapy and/or had developed acute leukemia prior to the initial cytogenetic analysis. The pattern of the chromosome rearrangements in our series is in agreement with the karyotypic findings in the 411 previously reported cases of CMPD. Trisomy 8 and 9 and del(20q) dominate in PV. The picture in MFS is more heterogenous with several aberrations, dup(1q), -5, del(5q), -7, del(7q), +8, +9, del(13q), del(20q), and +21, found equally frequently. No pathognomonic chromosome aberration has been detected in IT, but t(9;22) occurs more often than other changes. Thus, although a non-random cytogenetic pattern is discernible in CMPD, there is considerable overlap both with other myeloid malignancies and among the different CMPD subtypes.

Adult↗