bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental origin of de novo chromosome 9 deletions in del(9p) syndrome
Authors: Micale Mark A. , Haren J. Marie , Conroy Jeffrey M. , Crowe Carol A. , Schwartz Stuart 
Published: June 2005

AbstractParental origin of de novo deletions in the short arm of chromosome 9 in patients with a clinical diagnosis of del(9p) syndrome was assessed in 13 patients using polymerase chain reaction (PCR) analysis of highly polymorphic dinucleotide repeat micro‐satellite markers located in the putative deleted region. The deletion was found to be of paternal origin in 9 cases and of maternal origin in the remaining 4 cases, suggesting that the molecular event resulting in the deletion occurs in both male and female gametogenesis and that genomic imprinting does not appear to play a role in the patho‐genesis of del(9p) syndrome. © 1995 Wiley‐Liss, Inc.
Hands and feet in the Apert syndrome
Authors: Cohen M. Michael , Kreiborg Sven 
Published: June 2005

AbstractWe studied 44 pairs of hands and 37 pairs of feet in Apert syndrome, utilizing clinical, dermatoglyphic, and radiographic methods. We also studied histologic sections of the hand from a 31‐week stillborn fetus. Topic headings discussed include: clinical classification of syndactyly; correlations between types of hands and feet in the same patient; dermatoglyphics; anatomy of the hand; radiologic assessment; comparison with other studies; histologic assessment of the hand; acrocephalosyndactyly vs. acrocephalopoly‐syndactyly: a pseudodistinction; and some generalizations. © 1995 Wiley‐Liss, Inc.
Diaphragmatic hernia in Denys‐Drash syndrome
Authors: Devriendt Koenraad , Deloof Els , Moerman Philippe , Legius Eric , Vanhole Chris , De Zegher Francis , Proesmans Willem , Devlieger Hugo 
Published: June 2005

AbstractWe report on a newborn infant with male pseudohermaphroditism and glomerular lesions (Denys‐Drash syndrome) but without Wilms tumor. A constitutional heterozygous mutation in the WT1 gene (366Arg to His) was identified. In addition the child had a large diaphragmatic hernia, so far not described in Denys‐Drash syndrome. The expression of the WT1 gene in pleural and abdominal mesothelium and the occurrence of diaphragmatic hernia in transgenic mice with a homozygous WT1 deletion strongly suggests that the diaphragmatic hernia in this patient is part of the malformation pattern caused by WT1 mutations. © 1995 Wiley‐Liss, Inc.
Spectrum of X‐linked hydrocephalus (HSAS), MASA syndrome, and complicated spastic paraplegia (SPG1): Clinical review with six additional families
Authors: Schrander‐Stumpel Constance , Höweler Chris , Jones Marilyn , Sommer Annemarie , Stevens Cathy , Tinschert Sigrid , Israel Jeanette , Fryns Jean Pierre 
Published: June 2005

AbstractX‐linked hydrocephalus (HSAS) (MIM *307000), MASA syndrome (MIM *303350), and complicated spastic paraplegia (SPG1) (MIM *312900) are closely related. Soon after delineation, SPG1 was incorporated into the spectrum of MASA syndrome. HSAS and MASA syndrome show great clinical overlap; DNA linkage analysis places the loci at Xq28. In an increasing number of families with MASA syndrome or HSAS, mutations in L1CAM, a gene located at Xq28, have been reported. In order to further delineate the clinical spectrum, we studied 6 families with male patients presenting with MASA syndrome, HSAS, or a mixed phenotype. We summarized data from previous reports and compared them with our data. Clinical variability appears to be great, even within families. Problems in genetic counseling and prenatal diagnosis, the possible overlap with X‐linked corpus callosum agenesis and FG syndrome, and the different forms of X‐linked complicated spastic paraplegia are discussed. Since adducted thumbs and spastic paraplegia are found in 90% of the patients, the condition may be present in males with nonspecific mental retardation. We propose to abandon the designation MASA syndrome and use the term HSAS/MASA spectrum, incorporating SPG1. © 1995 Wiley‐Liss, Inc.
Neuronal ceroid‐lipofuscinoses in Italy: An epidemiological study
Authors: Cardona Francesco , Rosati Elisabetta 
Published: June 2005

AbstractTo establish the incidence of neuronal ceroid‐lipofuscinoses (NCL) in Italy, we sent a questionnaire to all Neuropediatric and Child Neuropsychiatric Departments (answer rate 15/34 = 44%). Diagnoses were accepted only when based on firm clinical and/or electron microscopic criteria. We collected 58 cases born between 1966–1991 (2 infantile NCL, 37 late infantile NCL, and 19 juvenile NCL). The incidence was calculated only on patients born between 1974–1984.In this period, the incidence of overall NCL in the Italian population was calculated to be 0.56 per 100,000 live births (0.36 for late infantile NCL, and 0.20 for juvenile NCL).Our data show that infantile NCL is very rare in Italy, and that late infantile seems to be the most frequent form of NCL. © 1995 Wiley‐Liss, Inc.
Tissue culture loading test with storage granules from animal models of neuronal ceroid‐lipofuscinosis (Batten disease): Testing their lysosomal degradability by normal and Batten cells
Authors: Elleder M. , Drahota Z. , Lisá V. , Mareč Vl. , Mandys V. , Müller J. , Palmer D. N. 
Published: June 2005

AbstractStorage granules (SGs) from ovine and canine models of Batten disease were found to be easily phagocytosed by four cell types studied. The cell types tested were human fibroblasts and peripheral monocytes (control and from a late infantile Batten disease patient), rat C6 cell line, and neonatal cardiomyocytes. The phagocytosed SGs elicited an increase in acid phosphatase activity which was localized in the phagolysosome. After phagocytosis SGs were followed for various times ranging from 7 to 21 days and were found to be of unchanged density (phase contrast), autofluorescence, and ultrastructural appearance. These findings point to their undegradability, or very low degree of degradability, in phagolysosomes in both normal or Batten cultured cells. The Batten disease SGs are not toxic and did not cause any adverse affect on the host cells. Either the normal clearance rate from lysosomes is too slow to be measured by this technique or subunit c accumulation in lysosomes need not result from a primary lysosomal protease defect. Subunit c may aggregate, because of the lack of some normally preventive factor, resulting in a physical barrier to the degradation of this highly apolar molecule. © 1995 Wiley‐Liss, Inc.
Diagnoses of neuronal ceroid‐lipofuscinosis by immunochemical methods
Authors: Hosain Syed , Kaufmann Walter E. , Negrin Gisela , Watkins Paul A. , Siakotos Aristotle N. , Palmer David N. , Naidu SakkuBai 
Published: June 2005

AbstractThe neuronal ceroid‐lipofuscinoses (NCL), also known as Batten disease, are a not uncommon group of disorders affecting infants, children, and young adults. The abnormal ultrastructural profiles seen in NCL are used for standard diagnosis; however, they can be missed, and are also found in other neurodegenerative conditions. Furthermore, there is an overlap between the types of inclusion profiles among the different forms of NCL. Therefore, a more specific and biochemically‐based marker is necessary to confirm the diagnosis of NCL. Antibodies raised against the storage material from the ovine form of NCL (mitochondrial ATP synthase subunit c) were utilized to determine whether NCL could be distinguished from other metabolic‐neurodegenerative disorders. By immunoblotting and immunohistochemistry, several brain samples of well‐evaluated NCL cases confirmed increased accumulations in all NCL cases except in the brain of an infantile‐onset NCL patient. The immunoblot studies of skin fibroblasts and brain were sensitive but not highly specific to NCL, due to the recognition of this material in normal controls as well as in other neurogenetic diseases. Immunocytochemistry of skin fibroblasts clearly distinguished LINCL and JNCL cases from controls, and with further refinement has the potential for becoming a diagnostic tool. © 1995 Wiley‐Liss, Inc.
Early detection of canine ceroid‐lipofuscinosis (CCL): An ultrastructural study
Authors: Savill J. , Azzarelli B. , Siakotos A. N. 
Published: June 2005

AbstractEnglish setters from the Koppang line have been used as a model for the juvenile type of Batten disease in human patients. This disorder, canine ceroid‐lipofuscinosis (CCL), has been shown by Koppang [1973: Mech Ageing Dev 2:421–445] to be an autosomal recessive disorder. Homozygous animals show the typical storage granules by autofluorescence; however, the autofluorescence material cannot easily be detected in affected dogs before age 3–6 months. At the present time the early stages of CCL can be studied only in litters from homozygous matings. Electron microscopy was used to study the reliability of diagnosing affected animals in heterozygous‐heterozygous (HET‐HET) and heterozygous‐homozygous (HET‐HOM) litters at age 2–3 weeks. The electron micrographs of brain biopsies were examined and the number of all dense bodies (d.b.), including linear and fingerprint patterns typical of CCL, were counted per neuron. The results indicated that affected animals have higher numbers of dense bodies than nonaffected carriers. Four‐6 months later confirmatory diagnoses were made on a second contralateral biopsy taken and examined as a frozen section by autofluorescence. The diagnoses made by electron microscopy at age 2–3 weeks appeared identical to the results obtained by autofluorescence at 4–6 months of age. © 1995 Wiley‐Liss, Inc.
Abnormal degradative pathway of mitochondrial ATP synthase subunit c in late infantile neuronal ceroid‐lipofuscinosis (Batten disease)
Authors: Ezaki Junji , Wolfe Leonhard S. , Ishidoh Kazumi , Kominami Eiki 
Published: June 2005

AbstractSubunit c is normally present as an inner mitochondrial membrane component of the F0 sector of the ATP synthase complex, but in the late infantile form of neuronal ceroid‐lipofuscinosis (NCL) it was also found in lysosomes in high concentrations. The rate of degradation of subunit c as measured by pulse–chase and immunoprecipitation showed a marked delay of degradation in patients' fibroblasts with late infantile form of NCL. There were no significant differences between control cells and cells with disease in the degradation of cytochrome oxidase subunit IV, an inner membrane protein of mitochondria. Measurement of labeled subunit c in mitochondrial and lysosomal fractions showed that the accumulation of labeled subunit c in the mitochondrial fraction can be detected before lysosomal appearance of radioactive subunit c, suggesting that subunit c accumulated as a consequence of abnormal catabolism in the mitochondrion and is transferred to lysosomes through an autophagic process. The biosynthetic rate of subunit c and mRNA levels for P1 and P2 genes that code for it were almost the same in both control and patient cells. These findings suggest that a specific failure in the degradation of subunit c after its normal inclusion in mitochondria and its consequent accumulation in lysosomes. © 1995 Wiley‐Liss, Inc.
Refined localization of the Batten disease gene (CLN3) by haplotype and linkage disequilibrium mapping to D16S288‐D16S383 and exclusion from this region of a variant form of Batten disease with granular osmiophilic deposits
Authors: Mitchison H. M. , O'Rawe A. M. , Lerner T. J. , Taschner P. E. M. , Schlumpf K. , D'Arigo K. , de Vos N. , Gormally E. , Phillips H. A. , Thompson A. D. , Haines J. L. , Hart Y. M. , Andermann E. , Callen D. F. , Breuning M. H. , Gardiner R. M. , Mole S. E. 
Published: June 2005

AbstractHaplotype analysis in a collaborative collection of 143 families with juvenile‐onset neuronal ceroid lipofuscinosis (JNCL) or Batten (Spielmeyer‐Vogt‐Sjögren) disease has permitted refined localization of the disease gene, CLN3, which was assigned to chromosome 16 in 1989. Recombination events in four maternal meioses delimit new flanking genetic markers for CLN3 which localize the gene to the chromosome interval 16p12.1‐11.2 between microsatellite markers D16S288 and D16S383. This narrows the position of CLN3 to a region of 2.1 cM, a significant reduction from the previous best interval. Using haplotypes, analysis of the strong linkage disequilibrium that exists between genetic markers within the D16S288‐D16S383 interval and CLN3 shows that CLN3 is in closest proximity to loci D16S299 and D16S298. Analysis of markers across the D16S288‐D16S383 region in four families with a variant form of JNCL characterized histologically by cytosomal granular osmiophilic deposits (GROD) has excluded linkage of the gene locus to the CLN3 region of chromosome 16, suggesting that JNCL with GROD is not an allelic form of JNCL. © 1995 Willy‐Liss, Inc.
Interest in genetic testing among first‐degree relatives of breast cancer patients
Authors: Lerman Caryn , Seay Janet , Balshem Andrew , Audrain Janet 
Published: June 2005

AbstractThe recent cloning of a breast‐ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first‐degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta =.15; P,.0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations. Prior to widespread availability of such testing, it will be critical to develop informed consent protocols to educate individuals about the benefits and limitations of predictive testing for this multifactorial disease. © 1995 Wiley‐Liss, Inc.
Previously apparently undescribed syndrome: Shallow orbits, ptosis, coloboma, trigonocephaly, gyral malformations, and mental and growth retardation
Authors: Ramer Jeanette C. , Lin Angela E. , Dobyns William B. , Winter Robin , Aymé Ségolène , Pallotta Rosanna , Ladda Roger L. 
Published: June 2005

AbstractWe describe 2 children with severe ptosis, trigonocephaly, broad nasal bridge, and major brain malformation. A total of 8 children have been reported who share most of these findings. Two of the individuals have had identical pericentric inversions involving chromosome 2p12–ql4. These cases appear to represent a unique malformation syndrome. © 1995 Wiley‐Liss, Inc.
Combined Leydig cell and Sertoli cell dysfunction in 46, XX males lacking the sex determining region Y gene
Authors: Turner Bryan , Fechner Patricia Y. , Fuqua John S. , Marcantonio Sandra M. , Periman Elizabeth J. , Vordermark Jonathan S. , Berkovitz Gary D. 
Published: June 2005

AbstractWe have evaluated 3 individuals with a rare form of 46, XX sex reversal. All of them had ambiguous external genitalia and mixed wolffian and mullerian structures, indicating both Leydig cell and Sertoli cell dysfunction, similar to that of patients with true hermaphroditism. However, gonadal tissue was not ovotesticular but testicular with varying degrees of dysgenesis.SRY sequences were absent in genomic DNA from peripheral leukocytes in all 3 subjects. Y centromere sequences were also absent, indicating that testis development did not occur because of a low level mosaicism of Y bearing cells. The subjects in this report demonstrate that there is a continuum in the extent of testis determination in SRY‐negative 46, XX sex reversal, ranging from nearly normal to minimal testicular development. © 1995 Wiley‐Liss, Inc.
Splicing mutation in CYP21 associated with delayed presentation of salt‐wasting congenital adrenal hyperplasia
Authors: Kohn Brenda , Day Darren , Alemzadeh Ramin , Enerio Devi , Patel Sanjivan V. , Pelczar Joseph V. , Speiser Phyllis W. 
Published: June 2005

AbstractPatients with salt‐wasting congenital adrenal hyperplasia (SW‐CAH) most commonly carry an A‐G transition at nucleotide 656 (nt 656 A→G), causing abnormal splicing of ex‐ons 2 and 3 in CYP21, the gene encoding active steroid 21‐hydroxylase. Affected infants are severely deficient in cortisol and aldo‐sterone, and usually come to medical attention during the neonatal period. We report on 2 affected boys, homozygous for the nt 656 mutation, who thrived in early infancy, but suffered salt‐wasting crises unusually late in infancy, at 3.5 and 5.5 months, respectively. Laboratory studies at presentation showed hyponatremia, hyperkalemia, dehydration, and acidosis; serum aldo‐sterone was low in spite of markedly elevated plasma renin activity. Basal 17‐hydroxyprogesterone levels were only moderately elevated, yet the stimulated levels were more typical of severe, classic CAH due to 21‐hydroxylase deficiency. Genomic DNA from the patients was analyzed. Southern blot showed no major deletions or rearrangements. CYP21 ‐specific amplification by polymerase chain reaction, coupled with allele‐specific hybridization using wild‐type and mutant probes at each of 9 sites for recognized disease‐causing mutations, revealed a single, homozygous mutation in each patient: nt 656 A→G. These results were confirmed by sequence analysis. We conclude that the common nt 656 A→G mutation is sometimes associated with delayed phenotypic expression of SW‐CAH. We speculate that variable splicing of the mutant CYP21 may modify the clinical manifestations of this disease. © 1995 Wiley‐Liss, Inc.
Oculodentodigital dysplasia with cerebral white matter abnormalities in a two‐generation family
Authors: Norton Karen K. , Carey John C. , Gutmann David H. 
Published: June 2005

AbstractOculodentodigital dysplasia (ODDD) is an autosomal dominant disorder involving eye and face abnormalities, syndactyly, and enamel hypoplasia. Some individuals with ODDD also have spastic paraparesis. Previously, we reported on a woman with sporadic ODDD and progressive neurologic dysfunction who had cerebral white matter abnormalities demonstrated by magnetic resonance imaging (MRI). We now describe a 2‐generation family with ODDD and progressive paraparesis associated with leuko‐dystrophic changes documented by MRI. This family represents one of the largest pedigrees with ODDD described so far. The presence of abnormal white matter changes in both sporadic and inherited forms of ODDD suggests that the phenotype of ODDD should be expanded to include spastic paraparesis. © 1995 Wiley‐Liss, Inc.
Analysis of variability of clinical manifestations in Waardenburg syndrome
Authors: Reynolds Jennifer E. , Meyer Joanne M. , Landa Barbara , Stevens Cathy A. , Arnos Kathleen S. , Israel Jamie , Marazita Mary L. , Bodurtha Joann , Nance Walter E. , Diehl Scott R. 
Published: June 2005

AbstractExpression of clinical findings of Waardenburg syndrome type 1 (WS1) and type 2 (WS2) is extremely variable. Using our collection of 26 WS1 and 8 WS2 families, we analyzed the occurrence, severity, and symmetry of clinical manifestations associated with WS. We found significant differences between WS1 and WS2 in deafness, and in pigmentary and craniofacial anomalies. Factor analysis was used to identify manifestations which covaried, resulting in 2 orthogonal factors. Since mean factor scores were found to differ when compared between WS1 and WS2, we suggest that these factors could be useful in distinguishing WS types. We found that the WS gene was transmitted from mothers more often than from fathers. We also extensively examined the W‐Index, a continuous measure of dystopia canthorum. Our data suggest that use of the W‐Index to discriminate between affected WS1 and WS2 individuals may be problematic since 1) ranges of W‐Index scores of affected and unaffected individuals over‐lapped considerably within both WS1 and WS2, and 2) a considerable number of both affected and unaffected WS2 individuals exhibited W‐index scores consistent with dystopia canthorum. Misclassification of families may have implications for risk assessment of deafness, since WS2 families have been reported to have greater incidence of deafness, as confirmed in our study. © 1995 Wiley‐Liss, Inc.
Preliminary phenotypic map of chromosome 4p16 based on 4p deletions
Authors: Estabrooks Laurel L. , Rao Kathleen W. , Driscoll Deborah A. , Crandall Barbara F. , Dean John C. S. , Ikonen Elina , Korf Bruce , Aylsworth Arthur S. 
Published: June 2005

AbstractWe have collected and analyzed clinical information from 11 patients with chromosome 4p deletions or rearrangements characterized by various molecular techniques. Comparing the extent of these patients' deletions with their respective clinical presentations led to the proposal of a preliminary phenotypic map of chromosome 4p. This map consists of regions which, when deleted, are associated with specific clinical manifestations. Nonspecific changes such as mental and growth retardation are not localized, and probably result from the deletion of more than one gene or region. The region associated with most of the facial traits considered typical in Wolf‐Hirschhorn syndrome (WHS) patients coincides with the currently proposed WHS critical region (WHSCR), but some anomalies commonly seen in WHS appear to map outside of the WHSCR. The observation of clinodactyly in 2 patients with nonoverlapping deletions allows assignment of these defects to at least 2 separate regions in 4p16. These initial observations and attempts at genotype/phenotype correlation lay the groundwork for identifying the genetic basis of these malformations, a common objective of gene mapping efforts and chromosome deletion studies. © 1995 Wiley‐Liss, Inc.
Gonadal dysgenesis in del(18p) syndrome
Authors: Telvi Louise , Bernheim Alain , Ion Alexandra , Fouquet Françoise , Bouc Yves Le , Chaussain Jean‐Louis 
Published: June 2005

AbstractWe report on a girl with syndromal gonadal dysgenesis and a de novo del(18p). Genetic factors controlling gonadal development are located not only on the X chromosome, but also on autosomes. The present case suggests that one of these genes is situated on 18p. We conclude that patients with del(18p) syndrome should be evaluated for gonadal dysgenesis. © 1995 Wiley‐Liss, Inc.
Balanced reciprocal translocation mosaicism: How frequent?
Authors: Opheim Kent E. , Brittingham Allen , Chapman Douglas , Norwood Thomas H. 
Published: June 2005

AbstractWe describe 2 cases of balanced reciprocal translocation (BRT) mosaicism. The frequency of this aberration in the population referred to our laboratory was determined and compared to those frequencies reported in the literature by other clinical cytogenetics laboratories. The extent of BRT mosaicism was also examined in surveys of prenatal populations, which are less likely to have a bias due to ascertainment on the basis of abnormal phenotype. The frequencies in the postnatal and prenatal populations examined in this study were calculated to be 5.7 × 10−5 (95% confidence interval is 3.2–8.2 × 10−5) and 4.1 × 10−5 (95% confidence interval is 2.0–6.2 × 10−5). However, in view of the extent of variation reported in the various studies, these estimates should be considered first approximations of the true frequency. © 1995 Wiley‐Liss, Inc.