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E Fleischnick

Publications and source records attributed to E Fleischnick.

12 recordsLinked to original sources
PubMed1989

Extended major histocompatibility complex haplotypes in patients with multiple sclerosis.

We derived complete haplotypes of the major histocompatibility complex for 33 patients with MS and their families. The DR2 allele and DR2-bearing extended haplotypes, in proportion, were overrepresented on chromosomes of MS patients compared with parental chromosomes not transmitted to MS offspring. We did not confirm previous reports that particular alleles at the BF locus are overrepresented in MS or that C2 hypocomplementemia is present. These results suggest that the DR2 allele is a risk factor for MS, and not merely a genetic marker of the population of origin.

Alleles↗
PubMed1988

The distribution of human C4 DNA variants in relation to major histocompatibility complex alleles and extended haplotypes.

A C4 DNA polymorphism that can subdivide C4 allotypes and major histocompatibility complex-linked complement gene cluster allele combinations (complotypes) that are not distinguishable by standard electrophoretic means was used to assess further the distribution and linkage association of C4 variants. Segregation of the DNA polymorphism in family studies allowed assignment of particular variants to particular major histocompatibility complex haplotypes. These studies revealed that some complotypes were exclusively correlated with a particular C4 DNA variant, whereas others were not and could be subdivided according to which particular C4 DNA variant was observed. When complotypes that could be subdivided at the DNA level were considered in relation to flanking major histocompatibility complex markers, it was apparent that complotypes associated with major histocompatibility complex "extended haplotypes" had an exclusive correlation with a particular C4 DNA variant. This finding supports the hypothesis that "extended haplotypes" are unique associations of major histocompatibility complex allele combinations and are genetically similar, stably inherited units.

Alleles↗
PubMed1987

Extended major histocompatibility complex haplotypes in patients with gluten-sensitive enteropathy.

We have studied major histocompatibility complex markers in randomly ascertained Caucasian patients with gluten-sensitive enteropathy and their families. The frequencies of extended haplotypes, defined as haplotypes of specific HLA-B, DR, BF, C2, C4A, and C4B allelic combinations, occurring more frequently than expected, were compared on patient chromosomes, on normal chromosomes from the study families, and on chromosomes from normal families. Over half of patient chromosomes consisted almost entirely of two extended haplotypes [HLA-B8, DR3, SC01] and [HLA-B44, DR7, FC31] which, with nonextended HLA-DR7, accounted for the previously observed HLA markers of this disease: HLA-B8, DR3, and DR7. There was no increase in HLA-DR3 on nonextended haplotypes or in other extended haplotypes with HLA-DR3 or DR7. The distribution of homozygotes and heterozygotes for HLA-DR3 and DR7 was consistent with recessive inheritance of the major histocompatibility complex-linked susceptibility gene for gluten-sensitive enteropathy. On the other hand, by odds ratio analysis and from the sum of DR3 and DR7 homozygotes compared with DR3/DR7 heterozygotes, there was an increase in heterozygotes and a decrease in homozygotes suggesting the presence of modifying phenomena.

Celiac Disease↗
PubMed1987

The autosomal dominant form of "pure" familial spastic paraplegia: clinical findings and linkage analysis of a large pedigree.

We studied 33 affected members in a family with autosomal dominant "pure" familial spastic paraplegia (FSP). Symptoms began in the fourth or fifth decade, expression varied, and progression was slow. We excluded close linkage to the HLA locus (distal end of short arm of chromosome 6); C8 alpha-gamma locus (proximal end of short arm of chromosome 1); PGM1 (middle region of short arm of chromosome 1); and P blood group (location unknown). Although there was no statistically significant linkage between FSP and any of the other markers, lod scores were positive with loci for GC (vitamin D binding globulin) located on chromosome 4 (4q11-q13) and Rh located on chromosome 1 (1p34-p36).

Adolescent↗
PubMed1986

Tapetoretinal degeneration associated with multisystem abnormalities. A case report.

Tapetoretinal degeneration is not infrequently associated with other systemic abnormalities. The authors have examined an 11-year-old girl with severe pigmentary degeneration of the retina associated with severe musculoskeletal abnormalities, growth failure, recurrent respiratory problems, sensorineural hearing loss, and mental retardation. To the best of their knowledge, this constellation of features has not been described previously and probably represents a new clinical entity.

Abnormalities, Multiple↗
PubMed1985

Complotype genetic loci segregate more frequently with HLA-DR than with HLA-B.

The loci for BF, C2, C4A, and C4B are very closely linked to each other so that alleles of these plasma protein markers occur in populations in linkage disequilibrium and are inherited as single genetic units called complotypes. These complotypes are coded by a DNA region of the short arm of chromosome 6 embracing approximately 100 kilobases, which serve as a marker of the major histocompatibility complex. We have studied the complotypes of nine families with known HLA-B/DR crossovers. In seven families, the complotypes were inherited with HLA-DR, including in one family with a double recombination. The haplotype HLA-A28, Cw1, B27, FC3, 20, DR4 of JTr resulted from two recombinations between HLA-A2, Cw1, B27, SC42, DR7 and HLA-A28, Cwx or Cw1, B37, FC3, 20, DR4. In the remaining two families (Ro and Lo) the complotypes were inherited with HLA-B. The haplotype A2, Cw5, Bw44, SC30, DR3 of StLo resulted from paternal recombination between the haplotypes A2, Cw5, Bw44, SC30, DR4 and A24, B8, SC01, DR3, and the haplotype A24, Cw4, Bw35, SC31, DR3 of NaRo resulted from maternal recombination between A24, Cw4, Bw35, SC31, DR4 and A26, Bw41, FC31, DR3. Our data suggest that the complotype region maps closer to HLA-D than to HLA-B.

Complement C2↗
PubMed1984

DNA polymorphism of the C4 genes. A new marker for analysis of the major histocompatibility complex.

Polymorphisms of the proteins encoded by genes that lie within the major histocompatibility complex (MHC) have served as useful markers for organ transplantation and in genetic analysis of a large number of MHC-linked diseases. To extend the range of MHC polymorphic markers, we used a complementary-DNA probe specific for the fourth component of human complement (C4) to identify a new variant within the MHC. Polymorphic variants at the DNA level were detected among subjects with identical phenotypes of the corresponding protein. C4 genomic polymorphisms are inherited with the segment of the short arm of chromosome 6 that carries the HLA-DR and complement loci. The autosomal codominant mode of inheritance of this genetic marker and its utility for evaluation of 21-hydroxylase-deficiency congenital adrenal hyperplasia, one of the many MHC-linked diseases, were established.

Adrenal Hyperplasia, Congenital↗
PubMed1984

Pre-type 1 (insulin-dependent) diabetes: common endocrinological course despite immunological and immunogenetic heterogeneity.

In an ongoing prospective study 32 individuals have been evaluated for insulin secretory dynamics, islet cell antibodies and HLA antigens, during the preclinical phase of Type 1 diabetes mellitus. Twenty-four out of the 32 subjects were islet cell antibody-positive. To date, 14 subjects (10 islet cell antibody-positive, four islet cell antibody-negative) have progressed to develop overt diabetes. Several patterns of HLA-DR expression were noted (DR3/DR4, DR3/DR3, DR3/x, DR3/DR1, DR4/x, DR4/DR7, DR5/DR7, DR1/DR7 and DR1/DR2). Irrespective of differences in islet cell antibody status or HLA-DR alleles, pre-diabetic individuals exhibited a similar slow course of progressive beta-cell dysfunction.

Adolescent↗
PubMed1983

Extended MHC haplotypes in 21-hydroxylase-deficiency congenital adrenal hyperplasia: shared genotypes in unrelated patients.

HLA, complement, and glyoxalase I alleles were studied in 29 families in which at least one member has classical 21-hydroxylase-deficiency congenital adrenal hyperplasia. A rare complement allele, C4B*31, was found in over 20% of the haplotypes defined in these families and was always part of the complement haplotype BF*F, C2*C, C4A*Q0, C4B*31 (abbreviated FCO,31). The haplotype containing this rare set of complement alleles always carried the rare HLA allele, HLA-Bw47, usually carried HLA-A3, and almost always had the alleles HLA-Cw6, HLA-DR7, and the glyoxalase I (GLO) allele GLO1. Thus over 20% of the haplotypes in the population studied contained all or almost all of the rare extended haplotype HLA-(A3), Bw47, Cw6,DR7, FCO,31, GLO 1. 3 other haplotypes were each found twice in unrelated patients concordant for their disease phenotype and ethnic background. Extended MHC haplotypes may be markers for different genetic mutations causing 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Detection of late-onset 21-hydroxylase deficiency congenital adrenal hyperplasia in adolescents.

Because severe hirsutism is difficult to reverse, the evaluation of the adolescent girl with progressive hirsutism should aim at the pathophysiology of androgen excess in order to select appropriate therapies. A prospective study was undertaken to determine the occurrence of late-onset 21-hydroxylase deficiency among adolescents with androgen excess. Twenty-two young women (mean age 17.3 +/- 2.6 years) with androgen excess had serum 17-hydroxyprogesterone measured before and after bolus intravenous infusion of synthetic ACTH (Cortrosyn), 0.25 mg. Two patients, aged 13 and 19 years old, had elevated base line 17-hydroxyprogesterone and 30- and 60-minute responses to Cortrosyn consistent with 21-hydroxylase deficiency. Chromosome 6p haplotypes provided supportive evidence of 21-hydroxylase deficiency. The base line androgen levels, clinical presentation, and a four-day dexamethasone test did not distinguish patients with 21-hydroxylase deficiency from other hirsute adolescents. The Cortrosyn test identifies a population of adolescents who need long-term corticosteroid therapy. The use of major histocompatibility complex haplotypes could be of help in identifying affected siblings prior to the development of significant hirsutism.

Adolescent↗
PubMedDate not supplied

Progressive autoimmune beta cell insufficiency: occurrence in the absence of high-risk HLA alleles DR3, DR4.

In a prospective screening program for type I diabetes mellitus, we identified a unique family in which several members (mother and three siblings) expressed an unusual set of HLA-DR alleles (DR2+, DR3/4-) and were in different phases of immunologically mediated islet beta cell dysfunction. Immunologic and/or clinical manifestations of type I diabetes were absent in all siblings not sharing both HLA haplotypes in common with the proband. This article illustrates: the clinical utility of prospective family screening for predictive markers, such as islet cell antibodies, progressive autoimmune beta cell destruction can occur in the absence of the "high-risk" alleles HLA-DR3 and DR4, and HLA identity with the proband, rather than specific HLA alleles, i.e., presence of DR3, DR4 and absence of DR2, is an essential factor.

Adolescent↗