bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of the skeletal and immune systems
Authors: Hong Richard 
Published: June 2005

AbstractCertain disorders of the immune system seem to be associated with skeletal defects. The association was first recorded by McKusick et al. (Bulletin of the Johns Hopkins Hospital 116:285–326, 1964). A number of relationships between lymphocytes and osteocytes can be proposed. These include a common environment for development, common metabolic needs and effects upon osteocytes by products (cytokines) elaborated from lymphocytes or monocytes during immune responses. Thus, bony defects of varying degrees of severity are seen in short‐limb dwarfs, cartilage‐hair hypoplasia, and adenosine deaminase (ADA) deficiency. Cytokine activation of osteoclasts accounts for the lytic lesions seen in malignancies and the excessive bone resorption which accompanies autoimmune disorders such as rheumatoid arthritis.Correction of primary immune deficiency is accomplished by bone marrow transplantation. If the bony abnormality is subtle (as in some cases of ADA deficiency) the skeletal problem is resolved; if the bone defect is major as in short‐limb dwarfism, no improvement is seen.
Inherited disorders of collagen gene structure and expression
Authors: Byers Peter H. 
Published: June 2005

AbstractAs a result of investigations completed during the last 15 years, the molecular bases of most form of osteogenesis imperfecta (OI) and of some forms of the Ehlers‐Danlos syndrome (EDS) are now known. Most forms of OI result from point mutations in the genes (COL1A1 and COL1A2) that encode the chains of type I procollagen or mutations that affect the expression of these genes. Less frequently, mutations that affect the size of the chain can also result in these phenotypes. The phenotypic presentation appears to be determined by the nature of the mutation, the chain in which it occurs, and, for point mutations, the position of the substitution and the nature of the substituting amino acid in the protein product. Similar mutations in the gene (COL3A1) that encodes the chains of type III procollagen result in the EDS type IV phenotype. Mutations which result in deletion of the cleavage site for the aminoterminal procollagen protease result in the EDS type VII phenotype and other mutations which affect the structure of the triple‐helical domain by deletions and alter the conformation of the substrate at the site of proteolytic conversion can produce mixed phenotypes. Alterations in post‐translational processing of collagenous proteins can result in the EDS type VI and EDS type IX phenotypes. Linkage analysis and study of type II collagen proteins from individuals with a variety of skeletal dysplasias suggest that similar mutations in these genes also result in clinically apparent phenotypes. Mutations in the majority of the 20 known collagen genes have not yet been identified.
Statistical approaches for the detection of heterozygotes for biotinidase deficiency
Authors: Weissbecker Karen A. , Nance Walter E. , Eaves Lindon J. , Piussan Charles , Wolf Barry 
Published: June 2005

AbstractWe applied and evaluated 3 statistical approaches for the detection of heterozygotes for biotinidase deficiency in a randomly selected population of French adults. The first method, which used a cutoff value to dichotomize the population, lacked sensitivity. The second approach calculated the probability of heterozygosity for a given enzyme activity through the application of Bayes theorem to the normal density functions of the enzyme distributions of the obligate heterozygote and the test populations. A priori values of the means and standard deviations (SDs) of the genotypic distributions were used. This method was sufficiently sensitive for both population screening and genetic counseling, but requires prior knowledge of the frequency of the deficient gene (q). The third approach was similar to the second, however, maximum likelihood estimates of the means and SDs of the genotypic distributions were calculated and used to determine the probability of heterozygosity for a given enzyme activity. This method was as sensitive as the second method and is appropriate for screening populations for which there is little prior information about the gene frequency and the genotypic distributions. This method can also be used to estimate the gene frequency of the disorder within a given ethnic or racial population. Using this method, we estimated the frequency of heterozygotes (2pq) in the French population to be 0.012, which was similar to that estimated from the results of neonatal screening for biotinidase deficiency. These methods can be used to detect heterozygotes and to estimate the gene frequency of other inherited enzyme deficiencies.
Complementation by two non‐homologous recombinant chromosomes 3
Authors: Allderdice P. W. , Ali M. , McAlpine P. J. 
Published: June 2005

AbstractThe first example known to us of complementation by two non‐homologous chromosomes 3 is present in the karyotype of a phenotypically normal brother of an inv(3)(p25q21) carrier. The normal chromosomes 3 are replaced by two complementary recombinant chromosomes 3. The longer recombinant duplicates 3q21‐qter and is deficient for 3p25pter. It is identical to the recombinant inherited by infants born with multiple congenital anomalies to inv(3)(p25q21) carriers. The shorter recombinant duplicates 3p25‐pter and is deficient for 3q21‐qter. This recombinant has previously been observed only in prometaphase spreads from sperm of an inv(3) carrier from the same kindred. Theoretically it is possible for the carrier of these complementary recombinant chromosomes 3 to produce sperm carrying either a normal 3, or the inversion 3, which could then fertilize an egg carrying a normal 3 followed by normal fetal development. However, the spouse of our propositus reported one first trimester spontaneous abortion, followed by no recognized pregnancy over the next 12 years of marriage.
Ullrich‐Turner syndrome in mother and daughter: Prenatal diagnosis of a 46, X, del(X)(p21) offspring from a 45, X mother with low‐level mosaicism for the del(X)(p21) in one ovary
Authors: Varela M. , Shapira E. , Hyman D. B. 
Published: June 2005

AbstractA woman with Ullrich‐Turner syndrome but with normal secondary sex characteristics became pregnant on two occasions (ages 23 and 24). She had a 45, X karyotype in 100/100 lymphocytes and 50/50 skin fibroblasts. The first pregnancy ended in a miscarriage at 2 months of gestation. In the second pregnancy cultured amniocytes showed a 46, X, del(X)(p21) karyotype. This pregnancy resulted in an apparently normal girl. Biopsies of the mother's ovaries were obtained at the time of cesarean section. Grossly the ovaries appeared normal, and histologically the number of primordial follicles appeared normal. In the right ovary, 5/100 cells were 46, X, del(X)(p21), while all 100 cells in the left ovary were 45, X.
Difference in early development of presumed monozygotic twins with Rett syndrome
Authors: Bruck Isac , Philippart Michel , Giraldi Dinarte , Antoniuk Sergio 
Published: June 2005

AbstractNormal early development has generally been insisted on as an essential criterion for the diagnosis of Rett syndrome. A new set of monozygotic female twins is reported. Twin 1 was considered to be abnormal from birth while delay was not suspected in twin 2 until she was about one year old. Some regression occurred during the second year in both twins, who are now clinically indistinguishable from each other at age 4 years. Other than a slight difference in head circumference at birth, no environmental factor which could account for the clinical difference has been identified.
Interstitial tandem direct duplication of the long arm of chromosome 4 (q23‐q27) and possible assignment of the structural gene encoding human aspartylglucosaminidase to this segment
Authors: Halal Fahed , Vekemans Michel , Chitayat David 
Published: June 2005

AbstractWe report on a girl with a previously undescribed de novo direct tandem duplication 4q involving the segment q23→q27. Clinical manifestations included postnatal growth and psychomotor retardation, microcephaly, hirsute forehead, epicanthic folds, strabismus, depressed nasal bridge, long philtrum, small mouth, tetralogy of Fallot, and sacral dimple. Her phenotype is compared with that of previously reported cases of duplication 4q. An increased activity of the enzyme aspartylglucosaminidase (AGA) in cultured fibroblasts was demonstrated. This suggests possible assignment of the AGA gene to the chromosomal segment 4q23→4q27.
Mouse major histocompatibility complex and lung development: Haplotype variation, H‐2 immunolocalization, and progressive maturation
Authors: Jaskoll Tina , Hu Ching‐Chung , Melnick Michael 
Published: June 2005

AbstractThe association of the mouse major histocom‐patibility complex (H‐2), lung maturation, and corticosteroid responsiveness has recently been demonstrated in congenic B10 (H‐2b) and B10.A (H‐2a) mice (Hu et al.:American Journal of Medical Genetics 35:126–131, 1990). We have investigated additional haplotypes [B10.BR (H‐2k) and B10.D2 (H‐2d] to confirm that there is a strong association between H‐2 haplotype variation and the degree of pulmonary maturation. Lungs of B10.D2, B10.BR, B10, and B10.A congenic mice achieve haplotypic specific maturation:B10.D2 lungs > B10 lungs = B10.BR lung > B10.A lungs. It appears that the expression of these developmental potentials is under corticosteroid regulation. Further, to test the hypothesis that H‐2 antigens would be expressed earlier in embryonic lungs with the H‐2b (BIO) or H‐2k (B10.BR) haplotype than with the H‐2a (B10.A) haplotype, we investigated the spatiotemporal patterns of H‐2 antigen localization in B10, B10.BR, and B10.A congenic mouse strains with and without corticostroid treatment. The spatial patterns of H‐2 antigen localization was similar in the B10, B10.BR, and B10.A mouse lungs; however, these patterns appeared earlier in both untreated and treated B10 and B10.BR mice as compared with untreated B10.A mice, suggesting an H‐2 haplotype associated rate of pulmonary maturation. Following corticosteroid treatment, all congenic strains had a temporally comparable spatial distribution of H‐2 antigens. Our results provide preliminary evidence suggesting that both a lung “developmental gene(s)” and a “glucocorticoid responsiveness gene(s)” are most likely outside the K‐D subregions of the H‐2 complex. A model of the H‐2 regulation of lung maturation and corticosteroid responsiveness is discussed.
Biochemical and clinical characterization of prealbumin CHICAGO: An apparently benign variant of serum prealbumin (transthyretin) discovered with high‐resolution two‐dimensional electrophoresis
Authors: Harrison Harold H. , Gordon Edys D. , Nichols William C. , Benson Merrill D. 
Published: June 2005

AbstractWe report identification, biochemical, clinical, and genetic studies of an apparently benign, electrophoretic variant of serum prealbumin (PALB, transthyretin, TTR) in a North American kindred of Swedish ancestry. The variant polypeptide stems from a C to T point mutation in exon 4 which results in methionine instead of threonine at position 119 of the mature molecule. It was discovered incidentally in a girl with classic alpha‐1‐antitrypsin (A1AT) deficiency and her father during diagnostic A1AT phenotyping by ISO‐DALT high‐resolution two‐dimensional electrophoresis (2DE). Twelve relatives in the four‐generation paternal kindred, including five individuals who were heterozygous for the variant prealbumin, were studied. In each of these five heterozygotes, the variant allele product was equimolar and isoelectric with the normal protein, yet migrated with an apparently lower mass in the SDS‐PAGE dimension. The inheritance pattern was consistent with autosomal dominant transmission. Histories and physical examinations showed no evidence of amyloidosis, as has been observed with other variants of prealbumin. Mean values of serum prealbumin and retinol binding protein levels were higher in the carriers as compared to the normal relatives in the family, but the difference was not statistically significant. Thyroid hormone levels and distribution of thyroxine and triiodothyronine among binding proteins in serum were within reference limits. Four members of the lineage had dominant, scalp‐restricted keratinaceous cysts, yet only three of these four individuals had the variant. We counseled the family that this is likely a benign variant with regard to amyloidosis‐related morbidity or shortened life span, although senile effects cannot be entirely ruled out. The provisional designation assigned to this allele is PALBCHICAGO. The substitution of methionine at position 119, as predicted by the DNA sequence, was confirmed by amino acid sequencing of CNBr and tryptic peptides. This substitution occurs at a CpG dinucleotide that may be a point mutational “hot spot,” as has been postulated for the methionine‐30 and isoleucine‐122 PALB variants. The apparently lower mass of the variant probably results from a more compact conformation in SDS. With the exception of histidine‐58, a charge substitution, all other amyloidosis‐related prealbumin variant polypeptides had normal mobility in the ISODALT 2DE system.
Prenatal sonographic documentation of cystic hygroma regression in Noonan syndrome
Authors: Donnenfeld Alan E. , Nazir Munir A. , Sindoni Frank , Librizzi Ronald J. 
Published: June 2005

AbstractPrenatal diagnosis of a posterior nuchal cystic hygroma was made at 13 weeks of gestation in a fetus diagnosed at birth with Noonan syndrome. Through serial sonographic evaluation during pregnancy, the embryologic evolution of cystic hygroma into nuchal skin thickening was appreciated and later correlated with postnatal findings of nuchal skin fold redundancy and pterygium colli in a patient with Noonan syndrome. These observations support the concept of the jugular lymphatic disruption sequence as pathogenesis of the nuchal findings in severely affected Noonan syndrome patients.
Fat distribution in overweight patients with Ullrich‐Turner syndrome
Authors: Hanaki Keiichi , Ohzeki Takehiko , Ishitani Nobuo , Motozumi Hiroko , Matsuda‐Ohtahara Hiroko , Shiraki Kazuo 
Published: June 2005

AbstractOverweight patients with Ullrich‐Turner syndrome (UTS) and control children with similar weight/height and indices of overweight were studied to clarify the unique fat distribution in the syndrome. Triceps and ulnar skinfold thickness (SFT) in UTS patients was significantly less than that of obese children without the syndrome. The means of SFT at the subscapular and paraumbilical regions were also less in the patients than control girls, though significance was not documented. Thus, increased body weight in UTS children seems mainly to be due to excess of adipose tissue, not in the limbs but on the trunk, and/or due to the increment of lean body mass.
Dextrocardia, microphthalmia, cleft palate, choreoathetosis, and mental retardation in an infant born to consanguineous parents
Authors: Nachlieli Tal , Gershoni‐Baruch Ruth 
Published: June 2005

AbstractWe report on an infant (born to consanguineous parents) with an unusual face, microphthalmia, cleft palate, dextrocardia, choreoathetosis, and mental retardation. This child has many traits in common with an infant recently described by Aughton [1990] as a probable new syndrome.
Ventricular extrasystoles with syncopal episodes, perodactyly, and Robin sequence in three generations: A new inherited MCA syndrome?
Authors: Stoll Claude , Kieny Jean‐René , Dott Béatrice , Alembik Yves , Finck Sonya 
Published: June 2005

AbstractWe observed the combination of the Robin sequence with perodactyly (hypoplasia and/ or agenesis of the distal phalanx of the toes) and cardiac arrhythmia (ventricular extra‐systoles occurring as bigemini or multifocal tachycardia with syncopal episodes) in 6 relatives in 3 generations. This familial association has not been reported before and probably represents a previously unrecognized heritable malformation syndrome.
Molecular study of 45,X conceptuses: Correlation with clinical findings
Authors: Lorda‐Sanchez Isabel , Binkert Franz , Maechler Marco , Schinzel Albert 
Published: June 2005

AbstractThe parental origin of the single X in 45 cases (40 liveborns and 5 fetuses) with a 45, X karyo‐type was studied using polymorphic DNA probes. The single X was paternal in origin (Xp) in 10 cases (22.2%) and maternal (Xm) in 35 cases (77.8%). Y chromosome material was detected in 1 out of the 35 cases with a 45, Xm constitution. Analysis of parental ages and clinical data of the patients with respect to the origin of the single X revealed no significant differences between the origins.
Linkage map of the chromosomal region surrounding the infantile neuronal ceroid lipofuscinosis on 1p
Authors: Järvelä Irma , Santavuori Pirkko , Puhakka Lea , Haltia Matti , Peltonen Leena 
Published: June 2005

AbstractThe neuronal ceroid lipofuscinoses (NCLs) of childhood are divided into 3 main types according to age‐of‐onset, clinical course, and neurophysiological and neuropathological findings: infantile, late infantile, and juvenile. All forms are inherited as an autosomal recessive trait, and their biochemical background is still unknown. The infantile type (INCL) with the earliest age‐of‐onset and the most severe clinical course, occurs in Finland with an incidence of 1:20,000, i.e., 116 patients have been found in our country up to now, whereas only about 50 cases have been reported from other parts of the world.Earlier we reported the linkage of INCL to the short arm of chromosome 1. Here we describe a more precise linkage map of this area. Our current map places the INCL mutation between D1S57 and D1S79; D1S7 has so far shown no recombination events between the marker and the disease (lod score 4.55 at θ = 0.00). Our material includes 64% of all living patients in Finland, and no linkage disequilibrium of haplotypes is seen, using the 2 physically close markers D1S57 and D1S79. This finding as well as our LINKMAP analyses suggest that the distance between the disease locus and the flanking markers is about 3–4 cm.
Evidence for processing of dolichol‐linked oligosaccharides in patients with neuronal ceroid‐lipofuscinosis
Authors: Daniel Peter F. , Sauls Derrick L. , Boustany Rose‐Mary N. 
Published: June 2005

AbstractIn agreement with reports from other laboratories, we have shown that patients with the juvenile or late infantile forms of neuronal ceroid‐lipofuscinosis (NCL) have greatly increased levels (5‐fold to 20‐fold) of dolichyl pyrophosphoryl oligosaccharides in their cerebral gray matter. Oligosaccharides cont ain‐ing 2 GlcNAc residues and 3 to 9 mannose residues were liberated by mild acid hydrolysis. The oligosaccharide profile given by brain tissue from 2 patients with infantil e NCL was markedly different from that of late infantile and juvenile NCL brain, with Man9GlcNAc2 as the most abundant component and decreasing amounts of Man8‐ Man7‐and Man6GlcNAc2. By contrast, Man5GlcNAc2 was the most abundant oligosaccharide present in all juvenile NCL brain samples analyzed. Both the susceptibility of the isolated Man5GlcNAc2 to endoglucosaminidase H digestion and permethylation analysis clearly indicated that it is not an intermediate in the biosynthesis of Glc3Man9GlcNAc2‐PP‐dolichol but has undergone catabolism, probably either in the endoplasmic reticulum or in the Golgi apparatus. Treatment of cultured skin fibroblasts for 7 days with N‐methyldeoxyno‐jirimycin, a potent inhibitor of the endoplasmic reticulum processing enzymes glucosidase I and II, resulted in an accumulation of the same Man5GlcNAc2‐PP‐dolichol species that was elevated in juvenile NCL brain. The level in untreated fibroblasts was undetectable, suggesting that inhibition of processing glu‐ cosidases has interfered with the regulation and compartmentalization of lipid‐linked oli‐gosaccharides.
Niemann‐Pick type‐C disease: Deficient intracellular transport of exogenously derived cholesterol
Authors: Roff Calvin F. , Goldin Ehud , Comly Marcella E. , Blanchette‐Mackie Joan , Cooney Adele , Brady Roscoe O. , Pentchev Peter G. 
Published: June 2005

AbstractNPC disease is an autosomal recessive neurovisceral storage disorder. A pleiotropic array of secondary enzymatic and storage abnormalities has in the past obscured a cohesive understanding of the underlying metabolic basis of this disorder. Recent findings, reviewed in this report, demonstrate that NPC disease is a cholesterol lipidosis resulting from defective intracellular cholesterol transport. The sequence of cellular events characteristic of NPC is 1) deficient intracellular transport of exogenously derived cholesterol resulting in retarded induction of cellular cholesterol homeostatic regulation; 2) accumulation of cholesterol, in lysosomes; and 3) secondary cellular effects. Retarded esterification of exogenous cholesterol and accumulation of unesterified cholesterol in lysosomes is tightly coupled to the primary defect and serves as the basis for biochemical diagnosis of NPC.
Retina in various animal models of neuronal ceroid‐lipofuscinosis
Authors: Goebel Hans H. 
Published: June 2005

AbstractThe childhood forms of human neuronal ceroid‐lipofuscinosis (NCL) are invariably associated with a severe progressive retinopathy which commences at the photoreceptor level morphologically and proceeds to a final loss of neuronal cells accompanied by severe gliosis. In respective spontaneous animal conditions of NCL, in English setters, Dalmatian dogs, and New Zealand sheep, retinal involvement is not commensurate although the retina does not seem to be completely unaffected. In canine NCL, there might be functional and electro‐physiological impairment of retinal cells, but retinal atrophy is not obvious. In ovine NCL, the retina, apart from accumulating NCL‐specific lipopigments within neuronal perikarya, also shows loss of photoreceptors. Conversely, retinal pigment epithelial cells (RPE) in canine and ovine NCL contain peculiar lamellar inclusions, not seen in unaffected animals, possibly an indication of a disturbed phagocytic process of photoreceptor outer segments. Similar such lamellar inclusions have not been observed in RPE cells in human childhood NCL.
Mucopolysaccharidosis VII as cause of fetal hydrops in early pregnancy
Authors: Stangenberg Magnus , Lingman Göran , Roberts George , Ozand Pinar 
Published: June 2005

AbstractWe report on fetal hydrops presenting at 18 weeks of gestation and diagnosed as β‐glucuronidase deficiency. The parents were first cousins and there were 2 previous similar fetal deaths. β‐Glucuronidase was absent in cultured fetal fibroblasts and lymphoblasts but was normal in the tested relatives. The activities of other lysosomal enzymes were normal. © 1992 Wiley‐Liss, Inc.
Autosomal recessive cleft lip/palate, ectodermal dysplasia, and minor acral anomalies: Report of a Brazilian family
Authors: Richieri‐Costa Antonio , Guion‐Almeida Maria Leine , Freire‐Maia Newton , Pinheiro Marta 
Published: June 2005

AbstractWe report on a Brazilian woman, born to consanguineous (first cousin) parents (F = 1/16) and presenting cleft lip/palate, ectodermal dysplasia, interdigital webbing, and other malformations. Parental consanguinity and possible recurrence in sibs suggest autosomal recessive inheritance. The nosologic aspects with the Martinez syndrome and with the Zlotogora–Ogur syndrome are discussed. © 1992 Wiley‐Liss, Inc.