bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anthropometric characteristics of X‐linked hypophosphatemia
Authors: Pronicka Ewa , Popowska Ewa , Rowińska Elżbieta , Arasimowicz Elżbieta , Syczewska Małgorzata , Jurkiewicz Dorota , Lebiedowski Michał 
Published: March 2004

AbstractAn anthropometric study was undertaken to assess head proportions of patients with X‐linked hypophosphatemia (XLH). Fourteen morphometric parameters of the head were measured and 10 cephalic indices calculated in 82 affected persons (57 females and 25 males) from 55 unrelated families with XLH, and compared with the results obtained in the group of their healthy relatives (37 females and 33 males), as well as with general population control values. Normalized values (SD, z‐score) were analyzed statistically. The group of healthy relatives, both males and females, differed significantly from Polish population control values in most of the normalized variables measured, making population control values useless as a control group for the analyzed XLH group. Intrafamilial values of cephalic parameters in healthy relatives of the XLH patients were finally applied for statistical analysis. Generally patients with XLH showed highly statistically significant increase in head length (males 0.95 ± 1.07 vs. −0.37 ± 1.02, females 0.57 ± 1.59 vs. −0.06 ± 1.15), significant decrease in occipital breadth (males −0.56 ± 1.27 vs. 0.70 ± 1.28, females −0.59 ± 1.7 vs. 0.13 ± 1.1) and several milder anomalies of craniofacial proportions. Mean cephalic index was significantly lower in XLH patients when compared with the healthy relatives (males −0.909 vs. 0.278 P < 0.0001, females −0.705 vs. 0.381 P = 0.007). The cephalic changes were found both in XLH children and XLH adults and were more pronounced in affected males than in females. There were no differences between offspring born by hypophosphatemic and normophosphatemic mothers. © 2003 Wiley‐Liss, Inc.
Attitudes and psychosocial adjustment of unaffected siblings of patients with phenylketonuria
Authors: Pho Lana T. , Zinberg Randi E. , Hopkins‐Boomer Theresa A. , Wallenstein Sylvan , McGovern Margaret M. 
Published: March 2004

AbstractSibling illness may contribute to an increased risk of adjustment problems in healthy siblings. Previous studies have reported a variety of effects on healthy individuals who have an ill sibling, but the psychosocial effects of treatable inherited disease on healthy siblings have not yet been investigated. We report the results of a survey study conducted in families with both unaffected and affected children with classic phenylketonuria (PKU), an inherited inborn error of metabolism. The survey included a knowledge test about PKU, and four previously validated instruments designed to assess psychosocial adjustment of unaffected siblings compared to age and sex matched norms. The responses revealed that unaffected adolescent and adult siblings had gaps in their knowledge about the genetic basis of PKU, and had evidence for the presence of adverse psychosocial sequelae. These findings suggest a role for genetic services providers, including genetic counselors, in assisting all members of a family adjust, when the diagnosis of an inborn error of metabolism has been made. © 2003 Wiley‐Liss, Inc.
A child with Angelman syndrome and trisomy 13 findings due to associated paternal UPD 15 and segmental UPD 13
Authors: Chun‐Hui Tsai Anne , Gibby Tamra , Beischel Linda , McGavran Loris , Johnson John P. 
Published: March 2004

AbstractA child with Angelman syndrome, cutis aplasia, cleft palate, and congenital microform cleft lip, born to a father with a Robertsonian translocation 13;15 is described. Molecular studies using polymorphic markers on chromosomes 15 and 13 showed paternal uniparental disomy (UPD) 15 and segmental UPD 13. © 2003 Wiley‐Liss, Inc.
Couples' experiences of predictive testing and living with the risk or reality of Huntington disease: A qualitative study
Authors: Richards Fiona 
Published: March 2004

AbstractA qualitative study, based on family systems theory, was undertaken in order to gain a better understanding of the impact of predictive testing and of living with the risk or reality of Huntington disease (HD), on couple relationships. Semi‐structured interviews were conducted with 14 couples; in 9 couples the at‐risk partner had undergone testing, and of these, 4 were already affected with HD. At‐risk partners in the remaining five couples had not been tested. Interview transcripts were analyzed to obtain a range of themes, which reflect the salient experiences of these couples in relation to HD. Most couples reported that receiving a predictive test result had little or no adverse effect on their relationship. However for two couples who separated after the at‐risk partner received a non‐carrier result, emotional factors associated with years of living with the HD risk, rather than the result itself, were regarded as having caused irreparable damage to the relationship. For two couples who have remained together since the diagnosis of one partner, loyalty was identified as the main factor contributing to the continuance of the relationship. The separations of the other two couples in which one partner was diagnosed were attributed to emotional distancing, and to the obsessive behavior of the affected partner. The findings of this study highlight both the individuality and the complexity of psychological effects on the intimate relationships of couples who live with the risk or reality of HD, and provide important insights for professionals offering support to these couples. © 2003 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of a de novo balanced X;autosome translocation: Evidence for predominant inactivation of the derivative X chromosome in a girl with multiple malformations
Authors: Gläser B. , Shirneshan K. , Bink K. , Wirth J. , Kehrer‐Sawatzki H. , Bartz U. , Zoll B. , Bohlander Stefan K. 
Published: March 2004

AbstractWe report on the characterization of a de novo, apparently balanced translocation t(X;15)(p11.3;q26) detected in a girl with multiple congenital malformations. Replication banding studies on Epstein–Barr virus transformed peripheral blood lymphocytes revealed non‐random X chromosome inactivation with predominant inactivation of the derivative X chromosome. Using chromosomal fluorescence in situ hybridization (FISH), we located the breakpoints to a 30 kb region on the short arm of the X chromosome band p11.3 and to a 160 kb region defined by BAC RP11‐89K11 on the long arm of chromosome 15. Our data suggest that the disruption/disturbance of plant homeo domain (PHD) zinc finger gene KIAA0215 or of another gene (RGN, RNU12, P17.3, or RBM10) in the breakpoint region on the X chromosome is not well tolerated and leads to the selection of cells with an active non‐rearranged X chromosome. © 2003 Wiley‐Liss, Inc.
Soft‐tissue facial areas and volumes in individuals with ectodermal dysplasia: A three‐dimensional non invasive assessment
Authors: Ferrario Virgilio F. , Dellavia Claudia , Serrao Graziano , Sforza Chiarella 
Published: March 2004

AbstractThe objective of this study was to supply quantitative information about the facial soft‐tissues of a group of patients with hypohidrotic ectodermal dysplasia. The three‐dimensional coordinates of 28 soft‐tissue facial landmarks were obtained by an electromagnetic digitizer in 11 male and 9 female patients with hypohidrotic ectodermal dysplasia aged 7–41 years, and in 318 healthy individuals of the same age, ethnicity, and sex. From the landmarks, facial areas (eyes, ears, nose, and lips) and volumes (nose and lips) were calculated according to a geometrical model of face. Data were compared to those collected in the normal subjects by computing z‐scores. Male and female z‐scores were not significantly different. In the pooled sample, the deviations from the norm were particularly evident in the lips, with a significant (Student's t‐test, P < 0.05) increment of the total lip area (mean z‐score: 0.96) and of the vermilion area of the upper lip (mean z‐score: 1.07), a finding negatively related (r = −0.632) to the number of teeth present in the mouth. The eye area was reduced in most patients, a finding significant on the left side (mean z‐score: −0.76). Most of the facial areas and volumes of the ectodermal dysplasia patients had z‐scores deviating only ±2 standard deviations from the reference groups. Only 4% of measurements had z‐scores larger than ±3. Additionally, a large inter‐individual variability was found, together with a certain age‐related trend of improvement of the number of measurements within the ±2 interval. The method allowed a simple, low cost, fast, and non invasive examination of the patients, and provided a quantitative assessment of the deviation from the norm. © 2003 Wiley‐Liss, Inc.
Cloacal exstrophy in an infant with 9q34.1‐qter deletion resulting from a de novo unbalanced translocation between chromosome 9q and Yq
Authors: Thauvin‐Robinet Christel , Faivre Laurence , Cusin Véronica , Khau Van Kien Philippe , Callier Patrick , Parker Keith L. , Fellous Marc , Borgnon Joséphine , Gounot Emmanuel , Huet Frédéric , Sapin Emmanuel , Mugneret Francine 
Published: March 2004

AbstractCloacal exstrophy is a rare malformation, belonging to a spectrum of birth defects, which, in order of severity, includes phallic separation with epispadias, pubic diastasis, bladder exstrophy, and cloacal exstrophy. This malformation overlaps the OEIS complex (O = omphalocele, E = bladder exstrophy, I = imperforate anus, S = spinal defects). The etiology of cloacal exstrophy is unknown to date. It may result from either a single defect of early blastogenesis or a defect of mesodermal migration during the primitive streak period. We report an infant with cloacal exstrophy, exomphalos, right kidney agenesis, ambiguous external genitalia, and axial hypotonia. The karyotype showed a de novo unbalanced translocation between the long arm of chromosome 9 and the long arm of chromosome Y resulting in a 9q34.1‐qter deletion. Reviewing the literature, we did not find any observation of cloacal exstrophy associated with a structural chromosomal abnormality. The steroidogenic factor 1 (SF1) gene, included in the deleted region, was a good candidate gene but no pathogenic mutation was found by direct sequencing. We hypothesize that another gene, expressed early in embryogenesis and responsible for cloacal exstrophy, is present in the 9q34.1‐qter region. © 2003 Wiley‐Liss, Inc.
Autosomal dominant inheritance of infantile myofibromatosis
Authors: Zand Dina J. , Huff Dale , Everman David , Russell Karen , Saitta Sulagna , McDonald‐McGinn Donna , Zackai Elaine H. 
Published: March 2004

AbstractWe present three families with infantile myofibromatosis (IM; OMIM no. 228550) inherited in an autosomal dominant (AD) manner. These three pedigrees prompted re‐assessment of pedigrees available within the genetic, oncologic, surgical, and pathologic literature, which suggest autosomal recessive (AR) inheritance. All familial IM may be interpreted as AD or, alternatively, there may be genetic heterogeneity for IM. As most nodules tend to regress spontaneously, familial history may be difficult to obtain and/or confirm. Clinical diagnosis and establishment of inheritance pattern can be important for prognosis and the recognition that other family members may be affected. © 2004 Wiley‐Liss, Inc.
Ala67Thr polymorphism in the Agouti‐related peptide gene is associated with inherited leanness in humans
Authors: Marks Daniel L. , Boucher Nathalie , Lanouette Christian‐Marc , Pérusse Louis , Brookhart Gregor , Comuzzie Anthony G. , Chagnon Yvon C. , Cone Roger D. 
Published: March 2004

AbstractA role for melanocortin signaling in the regulation of body weight in humans has been clearly established. Haploinsufficiency of the type 4 melanocortin receptor is associated with early‐onset obesity, implying that this receptor provides an important tonic inhibition of weight gain. Agouti‐related peptide (AGRP) is an endogenous antagonist of melanocortin signaling. Therefore, loss of AGRP function could lead to the expression of a lean phenotype. We investigated the potential role of AGRP in human weight regulation by examining the association between the Ala67Thr AGRP polymorphism and indices of body composition. Significant associations were found between homozygosity for this mutation (n = 8) and body composition phenotype in 874 subjects of the Quebec family study (QFS). By PCR‐RFLP analysis, we have identified eight individuals who are homozygous for the 67Thr variant allele within the QFS population, where none were observed in SAFHS. The eight QFS homozygote individuals have lower weight (−16%; P = 0.02), body mass index (−17%; P = 0.01), fat free mass (−9%; P = 0.002), fat mass (FM) (−20%; P = 0.04), and leptin (−20%; P = 0.02) when compared to those carrying at least one 67Ala allele. Individuals homozygous for the 67Thr allele had a BMI that was either at or slightly below an ideal range for their age. Thus, the Ala67Thr AGRP polymorphism is associated with lower body weight in humans, with the largest effect being observed on body FM. We did not observe any difference in the stability or cellular distribution of the mutant protein in a heterologous expression system, thus the mechanism of this effect requires further investigation. © 2004 Wiley‐Liss, Inc.
Ectopia lentis phenotypes and the FBN1 gene
Authors: Adès Lesley C. , Holman Katherine J. , Brett Maggie S. , Edwards Matthew J. , Bennetts Bruce 
Published: March 2004

AbstractMutations of the fibrillin‐1 (FBN1) gene on chromosome 15 have been described in patients with classical Marfan syndrome (MFS), neonatal MFS, the “MASS” phenotype, autosomal dominant ascending aortic aneurysms, autosomal dominant ectopia lentis (EL), Marfanoid skeletal features [Milewicz et al., 1995: J Clin Invest 95:2373–2378], familial arachnodactyly, Shprintzen–Goldberg syndrome [Hayward et al., 1994: Mol Cell Probes 8:325–327; Furthmayr and Francke, 1997: Semin Thorac Cardiovasc Surg 9:191–205], and severe progressive kyphoscoliosis [Adès et al., 2002: Am J Med Genet 109:261–270]. We report the use of denaturing high performance liquid chromatography (DHPLC) to facilitate the characterization of a previously elusive FBN1 mutation in the large autosomal dominant EL kindred described by Edwards et al. [1994: Am J Med Genet 53:65–71]. This isolated EL kindred remains the largest for which detailed clinical data is available. Nine years on, we present an update of the clinical status of the family. We report a recurrent FBN1 mutation, R240C, in the kindred. This mutation has been reported three times before, once in a family with classic MFS [Loeys et al., 2001: Arch Intern Med 161:2447–2454], once in one member of a multi‐generation EL kindred, [Körkkö et al., 2002: J Med Genet 39:34–41], and once in an adult from a familial EL kindred who had EL, and involvement of the integument, without cardiovascular involvement [Comeglio et al., 2002: Br J Ophthalmol 86:1359–1362]. This is the second report of the R240C mutation in association with isolated EL, and supports the existing evidence that the R240C mutation can result in two quite distinct, yet related, phenotypes. It also raises the possibility that R240C may prove to be a relative mutational “hot‐spot” for isolated EL. We review the current literature regarding EL (isolated and other) and FBN1 mutations. © 2003 Wiley‐Liss, Inc.
Death‐associated protein kinase expression in human temporal lobe epilepsy
Authors: Henshall David C. , Schindler Clara K. , So Norman K. , Lan Jing‐Quan , Meller Robert , Simon Roger P. 
Published: March 2004

AbstractExperimental and human data suggest programmed (active) cell death may contribute to the progressive hippocampal atrophy seen in patients with refractory temporal lobe epilepsy. Death‐associated protein (DAP) kinase is a novel calcium/calmodulin‐activated kinase that functions in apoptosis mediated by death receptors. Because seizure‐induced neuronal death involves both death receptor activation and calcium, we examined DAP kinase expression, localization, and interactions in hippocampal resections from patients with intractable temporal lobe epilepsy (n = 10) and autopsy controls (n = 6). Expression and phosphorylation of DAP kinase was significantly increased in epilepsy brain compared with control. DAP kinase and DAP kinase–interacting protein 1 (DIP‐1) localized to mitochondria in control brain, whereas levels of both were increased in the cytoplasm and microsomal (endoplasmic reticulum) fraction in epilepsy samples. Coimmunoprecipitation analysis showed increased DAP kinase binding to calmodulin, DIP‐1, and the Fas‐associated protein with death domain (FADD) in epilepsy samples. Finally, immunohistochemistry determined DAP kinase was coexpressed with DIP‐1 in neurons. This study provides the first description of DAP kinase and DIP‐1 in human brain and suggests DAP kinase is a novel molecular regulator of neuronal death in epilepsy. Ann Neurol 2004;55:000–000
Familial myopathy: New insights into the T14709C mitochondrial tRNA mutation
Authors: McFarland Robert , Schaefer Andrew M. , Gardner Julie L. , Lynn Stephen , Hayes Christine M. , Barron Martin J. , Walker Mark , Chinnery Patrick F. , Taylor Robert W. , Turnbull Douglass M. 
Published: March 2004

AbstractWe have defined the genetic defect in a large family first described in one of the earliest reports of suspected mitochondrial myopathy, as the mutation T14709C in the mitochondrial transfer RNAGlu (mt‐tRNAGlu) gene. Extraordinarily, this mutation has attained homoplasmy (100% mutated mt‐tRNAGlu) on at least three independent occasions in this family and has done so in one individual who remains asymptomatic with no clinical evidence of disease. Heteroplasmy (dual populations of mutated and wild‐type mtDNA) usually is regarded as one of the primary diagnostic criteria for pathogenicity and previous reports of the T14709C mutation detail heteroplasmy in a variety of tissues. In contrast, homoplasmy of mt‐tRNA mutations generally has been regarded as evidence of a benign nature, with rare exceptions that result in organ‐specific phenotypes. Discovering that T14709C, a common and severe mt‐tRNA mutation, can attain homoplasmy without symptoms or clinical signs of disease has profound implications for the identification and prevalence of other pathogenic mt‐tRNA mutations. Furthermore, variation in phenotype between homoplasmic individuals implies a crucial contribution from the nuclear genetic environment in determining the clinical outcome of mt‐tRNA mutations. Ann Neurol 2004;55:000–000
Relapsing and remitting multiple sclerosis: Pathology of the newly forming lesion
Authors: Barnett Michael H. , Prineas John W. 
Published: March 2004

AbstractThe study describes the clinical and pathological findings in 12 patients with relapsing and remitting multiple sclerosis, who died during or shortly after the onset of a relapse. Pathological changes not previously associated with the formation of new symptomatic lesions were observed in seven cases, namely, extensive oligodendrocyte apoptosis and microglial activation in myelinated tissue containing few or no lymphocytes or myelin phagocytes. No current laboratory model of multiple sclerosis, in particular, experimental allergic encephalomyelitis, is known with these features, which raises the possibility of some novel process underlying new lesion formation in multiple sclerosis. Ann Neurol 2004;55:000–000
Enzyme replacement therapy in late‐onset Pompe's disease: A three‐year follow‐up
Authors: Winkel Léon P. F. , Van den Hout Johanna M. P. , Kamphoven Joep H. J. , Disseldorp Janus A. M. , Remmerswaal Maaike , Arts Willem F. M. , Loonen M. Christa B. , Vulto Arnold G. , Van Doorn Pieter A. , De Jong Gerard , Hop Wim , Smit G. Peter A. , Shapira Stuart K. , Boer Marijke A. , Reuser Arnold J. J. , Van der Ploeg Ans T. , van Diggelen Otto P. 
Published: March 2004

AbstractPompe's disease is an autosomal recessive myopathy. The characteristic lysosomal storage of glycogen is caused by acid α‐glucosidase deficiency. Patients with late‐onset Pompe's disease present with progressive muscle weakness also affecting pulmonary function. In search of a treatment, we investigated the feasibility of enzyme replacement therapy with recombinant human α‐glucosidase from rabbit milk. Three patients (aged 11, 16, and 32 years) were enrolled in the study. They were all wheelchair‐bound and two of them were ventilator dependent with a history of deteriorating pulmonary function. After 3 years of treatment with weekly infusions of α‐glucosidase, the patients had stabilized pulmonary function and reported less fatigue. The youngest and least affected patient showed an impressive improvement of skeletal muscle strength and function. After 72 weeks of treatment, he could walk without support and finally abandoned his wheelchair. Our findings demonstrate that recombinant human α‐glucosidase from rabbit milk has a therapeutic effect in late‐onset Pompe's disease. There is good reason to continue the development of enzyme replacement therapy for Pompe's disease and to explore further the production of human therapeutic proteins in the milk of mammals. Ann Neurol 2004;55:000–000
Accelerated evolution of brain atrophy and “black holes” in MS patients with APOE‐ε4
Authors: Enzinger Christian , Ropele Stefan , Smith Stephen , Strasser‐Fuchs Siegrid , Poltrum Birgit , Schmidt Helena , Matthews Paul M. , Fazekas Franz 
Published: March 2004

AbstractApolipoprotein E (APOE)–ε4 has been associated with an unfavorable course of multiple sclerosis (MS). The mechanisms responsible for this are unclear, although cross‐sectional MRI demonstrated a higher extent of “black holes” (BHs) in such patients. Here, we have studied the impact of the APOE genotype on both the longitudinal evolution of focal (BH ratio) and global (brain volume change [BVC]) brain tissue damage. Ninety‐nine MS patients underwent ApoE genotyping, clinical examination, and magnetic resonance imaging at baseline and after 2.7 ± 1.1 years to assess lesion load (LL) and BVC. In APOE‐ε4 patients, the annual reduction in brain volume was fivefold higher (−0.65 ± 0.61%) than in those without APOE‐ε4 (−0.13 ± 0.36%; p = 0.0001). At baseline, T2 LL and T1 LL were non‐significantly higher in ε4 carriers, despite a shorter disease duration and absence of significant clinical differences. During follow‐up, T1 LL increased from 1.2 ± 2.3ccm to 1.7 ± 2.7ccm in the ε4 group, although T2 LL did not change, leading to a significantly higher increase in the BH ratio [(T1 LL/T2 LL) × 100] from 5.5 to 12.4% (p = 0.005). BH ratio remained almost constant in non‐ε4 patients (5.0 vs 5.7%). Accelerated brain tissue loss and a higher proportion of lesions evolving into BH therefore provide magnetic resonance imaging evidence for more pronounced tissue destruction in MS patients with APOE‐ε4. Ann Neurol 2004
Diffusion tensor fiber tracking shows distinct corticostriatal circuits in humans
Authors: Lehéricy Stéphane , Ducros Mathieu , Van De Moortele Pierre‐François , Francois Chantal , Thivard Lionel , Poupon Cyril , Swindale Nick , Ugurbil Kamil , Kim Dae‐Shik 
Published: March 2004

AbstractA landmark of corticostriatal connectivity in nonhuman primates is that cortical connections are organized into a set of discrete circuits. Each circuit is assumed to perform distinct behavioral functions. In animals, most connectivity studies are performed using invasive tracing methods, which are nonapplicable in humans. To test the proposal that corticostriatal connections are organized as multiple circuits in humans, we used diffusion tensor imaging axonal tracking, a new magnetic resonance technique that allows demonstration of fiber tracts in a noninvasive manner. Diffusion tensor imaging–based fiber tracking showed that the posterior (sensorimotor), anterior (associative), and ventral (limbic) compartments of the human striatum have specific connections with the cortex, and particularly the frontal lobes. These results provide the first direct demonstration of distinct corticostriatal connections in humans.