bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pigment variant of neuronal ceroid‐lipofuscinosis
Authors: Goebel Hans Hilmar , Gullotta Filippo , Bajanowski Thomas , Hansen Flemming Juul , Braak Heiko 
Published: June 2005

AbstractA 6‐year‐old girl had progressive ataxia, and visual disturbances resulting in blindness. She died in her sleep at age 22 years. She shared with her sister and paternal relatives bilateral pes cavus deformities and impaired deep‐tendon reflexes which suggested Charcot‐Marie‐Tooth disease. Her sister, who also had both polyneuropathy and a progressive central nervous system (CNS) disease, did not have pigmentary retinopathy. At autopsy, the patient was found to have neuronal ceroid‐lipofuscinosis (NCL) marked by intraneuronal accumulation of autofluorescent granular lipopigments in ballooned perikarya and conspicuous extraneuronal pigmentation of subcortical grey matter, but without axonal spheroids. These findings indicate a pigment variant of NCL and represent one of very few patients recorded. The ultrastructure of the intraneuronal pigments was uniformly granular, while that of the extraneuronal pigments found within processes of the neuropil and glial perikarya was more variegated.In addition to those patients with the pigment variant of NCL, described earlier by Jakob and Kolkmann [1973: Acta Neuropathol (Berl) 26:225–236], and Jervis and Pullarkat [1978: Neurology 28:500–503], our patient shared clinical symptoms with those described in a family afflicted with polyneuropathy and NCL by Wisniewski et al. [1987: J Child Neurol 2:33–41].Currently, it is unclear whether these families harbor different genetic diseases or whether they have similar atypical forms of juvenile NCL (JNCL). We conclude that the spectrum of pigment variants in lysosomal diseases is heterogeneous: only few and recently described patients have had NCL, while others most likely had other forms of lipidosis. © 1995 Wiley‐Liss, Inc.
Late onset juvenile neuronal ceroid‐lipofuscinosis with granular osmiophilic deposits (GROD)
Authors: Hofman Irene L. , Taschner Peter E. M. 
Published: June 2005

AbstractThe juvenile‐onset subtype of the neuronal ceroid lipofuscinoses (JNCL) is well known [Hofman, ISBN90‐71534‐19‐7 1990] and ultrastructurally characterized by fingerprints and/or curvilinear bodies in many cell types. Linkage studies indicated a most likely location for CLN3, the gene involved in JNCL, in the interval between loci D16S297 and D16S57, within close proximity of the loci D16S298 and D16S299 [Mitchison et al., Genomics 22:465–468, 1993].We present two sibs with a late onset progressive disease of mental deterioration, progressive macular degeneration, motor disturbances, and epilepsy. Histological symptoms of neuronal ceroid lipofuscinosis and ultrastructural granular osmiophilic deposits (GROD) in lymphocytes and neurons are found. Individual haplotypes at polymorphic marker loci on chromosome 16 were constructed to determine whether JNCL with GROD is linked to the CLN3 locus. © 1995 Wiley‐Liss, Inc.
Tissue and cellular distribution of subunit c of ATP synthase in Batten disease (neuronal ceroid‐lipofuscinosis)
Authors: Rowan Sarah A. , Lake B. D. 
Published: June 2005

AbstractThe major protein component of the storage bodies in the late infantile (LIB) and juvenile (JB) forms of Batten disease is subunit c of ATP synthase (subunit c). Ultrastructurally the stored material may appear as curvilinear bodies, fingerprint profiles, or a mixture of both, dependent upon the form of Batten disease and the cell type. The mnd/mnd mouse, an animal model for Batten disease, also stores subunit c and has loosely stacked lamellae within the neurons of the brain and in other cells and tissues. Using a range of tissue samples, immunolocalization, using avidin‐biotin techniques at the LM level and postembedding immunogold‐labelling (5 nm) with silver enhancement at the EM level, were used to investigate specific subunit c immunoreactivity. Subunit c storage was displayed in a number of cells, including neurons, muscle cells, adipocytes, macrophages, endothelial and some epithelial cells, and exocrine and endocrine cells. By EM, subunit c was localized to all curvilinear‐type storage bodies, but to nowhere else within the cell. It was not present over fingerprint profiles, the characteristic storage pattern of neurons within the JB gut, possibly due to steric factors. Preliminary studies in the mnd mouse showed subunit c immunoreactivity localized to storage profiles seen ultrastructurally in neurons of the brain, and liver and heart cells. We suggest that accumulation and distribution of subunit c within a variety of cell types, and its consistent absence in others, may be related to the particular cell type's longevity and its metabolic demand. © 1995 Wiley‐Liss, Inc.
Cellular distribution of lesions in Batten disease
Authors: Chronister Robert , Dyken Paul , Fields Phillip A. , Maertens Paul 
Published: June 2005

AbstractOne of the characteristic manifestations of chronic neuronal lipofuscinosis (Batten disease) is a marked predisposition for epileptic seizures. The management of these seizures is very difficult. The present study was initiated to determine what mechanisms could account for the seizure disorder. Tissue was examined from a patient with a history of Batten disease that was histologically verified. Reduced silver and Golgi impregnations were done on the parietal cortex of the patient. There was no evidence of the marked dendritic abnormalities seen in classic epileptic foci. Instead there was marked swelling and dilatation of the axon hillock and initial segment. This finding suggested that inhibition of these pyramidal neurons was markedly attenuated due to disruption of initial segment inhibitory synapses. Studies are continuing to determine if the GABA decreases seen in Batten disease may in part be due to trophic sequences brought about by loss of these critical inhibitory synapses. © 1995 Wiley‐Liss, Inc.
Decreasing hydraulic conductivity of Bruch's membrane: Relevance to photoreceptor survival and lipofuscinoses
Authors: Starita Carla , Hussain Ali A. , Marshall John 
Published: June 2005

AbstractDeterioration of visual performance leading to blindness is particularly severe in the early‐onset forms of Batten disease. Metabolic support of the neural retina is critically dependent on the choroidal blood supply and on efficient transport pathways through Bruch's membrane and the retinal pigment epithelium (RPE). Conversely, degradation products and, in particular, damaged membranous components of photoreceptor outer segments must be removed in the opposite direction. Incomplete breakdown of damaged “spent” discs leads to the age‐related accumulation of lipofuscin‐like pigments in the RPE, and these in turn influence the degenerative changes in Bruch's membrane. The generalized and extensive deposition of lipofuscin‐like material in Batten disease is therefore likely to exacerbate the degenerative changes in Bruch's membrane, and thereby compromise local fluid dynamics. The hydrodynamic properties of Bruch's membrane were examined in normal donor eyes and showed a precipitous decline of hydraulic conductivity during early life. In fact, the maximal capacity for fluid transport was halved for every 17 years of life. This finding is therefore highly relevant to the development of ensuing pathology in the neuronal ceroid‐lipofuscinoses. © 1995 Wiley‐Liss, Inc.
Sphingolipid activator proteins (SAPS) are stored together with glycosphingolipids in the infantile neuronal ceroid‐lipofuscinosis (INCL)
Authors: Tyynelä Jaana , Baumann Marc , Henseler Margarete , Sandhoff Konrad , Haltia Matti 
Published: June 2005

AbstractThe storage material isolated from the brains of patients with infantile neuronal ceroid‐lipofuscinosis (INCL) contains, on average, 43% protein and 35% lipids on a dry weight basis. Recently we identified the major storage proteins as sphingolipid activator proteins (SAPs) A and D by direct sequencing. In the present study we used monospecific anti‐sap‐B‐, anti‐sap‐C, and anti‐sap‐D‐antisera in immunohistochemical and Western analyses to show that sap‐D is, indeed, an integral component of the storage bodies. In contrast, no (or little) immunoreactivity for sap‐B or sap‐C was detected in the INCL storage granules. This observation is of interest for an understanding of the pathogenesis because the four SAPs are produced from a single precursor protein by proteolytic cleavage.Furthermore, we analysed the stored lipids on high performance thin layer chromatography combined with different staining techniques. In this preliminary analysis we found two glycosphingolipids, yet to be identified, to be common for all INCL patients. © 1995 Wiley‐Liss, Inc.
Genome‐wide search for CLN2, the gene causing late‐infantile neuronal ceroid‐lipofuscinosis (LNCL)
Authors: Haines J. L. , Boustany R.‐M. N. , Worster T. , Ter‐Minassian M. , Jondro P. , Lerner T. J. 
Published: June 2005

AbstractThe loci for the juvenile (CLN3) and infantile (CLN1) neuronal ceroid lipofuscinosis (NCL) types have been mapped by genetic linkage analysis to chromosome arms 16p and 1p, respectively. The late‐infantile defect CLN2 has not yet been mapped, although linkage analysis with tightly linked markers excludes it from both the JNCL and INCL loci. We have initiated a genome‐wide search for the LNCL gene, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 US families and 11 Costa Rican families. To date, we have completed typing with over 50 markers on chromosomes 2, 9, 13, and 18–22. The results of this analysis formally exclude about 10% of the human genome as the location of the LNCL gene. © 1995 Wiley‐Liss, Inc.
Michels syndrome in a Brazilian girl born to consanguineous parents
Authors: Guion‐Almeida M. L. , Rodini E. S. O. 
Published: June 2005

AbstractWe report on a Brazilian girl born to consanguineous parents and presenting with craniosynostosis, telecanthus, blepharophi‐mosis, blepharoptosis, epicanthus inversus, cleft lip and palate, skeletal defects, and hearing loss. This combination of anomalies appears to constitute the Michels syndrome. © 1995 Wiley‐Liss, Inc.
Nonspecific X‐linked mental retardation with macrocephaly and obesity: A further family
Authors: Baraitser M. , Reardon W. , Vijeratnam S. 
Published: June 2005

AbstractThe phenotypic nonspecificity of many forms of X‐linked mental retardation has hampered attempts to classify them into clinically homogeneous groups. One such condition, described by Clark and Baraitser [1987: Am J Med Genet 26:13–15], has been the subject of a single pedigree report to date. We now describe a further pedigree whose affected members share many manifestations with those reported by Clark and Baraitser, and we consider the possible distinction between this condition and Atkin‐Flaitz syndrome. © 1995 Wiley‐Liss, Inc.
Tel Aviv–Heidelberg three‐generation offspring study: Genetic determinants of apolipoprotein A1 and apolipoprotein B
Authors: Livshits G. , Blettner M. , Graff E. , Hoting I. , Wahrendorf J. , Brunner D. , Schettler G. 
Published: June 2005

AbstractThe contribution of major gene and multi‐factorial effects on variation of plasma apolipoproteins Al and B has been tested in a large sample of population‐based Israeli pedigrees. Our most parsimonious and best fitting model for both apolipoproteins is consistent with Mendelian transmissibility, with significant contribution of major genes (with 2 alleles recessive and dominant within each locus) and polygenes, but neglects effects of common sib environment as well as related intergeneration differences in polygenic effects. Total genetic effects explain 71 and 58% of phenotypic variance of APO‐A1 and APO‐B levels. The major genes account for about 44 and 32% of the variance in APO‐A1 and APO‐B, respectively, and the frequency of the recessive alleles determining the high level of apolipoproteins under the study in the Israeli population is in the vicinity of 40% at each locus. © 1995 Wiley‐Liss, Inc.
Follow‐up study in a patient with Setleis syndrome
Authors: Tsukahara Masato , Okabe Takahiro , Ohtsuka Morimasa , Furukawa Susumu 
Published: June 2005

AbstractWe report on an 8‐year‐old Japanese boy with Setleis syndrome. The patient had a very characteristic “coarse” facial appearance, bitemporal “forceps marks,” skin aplasia, sparse hair, and skin hypo‐ and hy‐perpigmentation. He also had previously undescribed manifestations, including an aberrant hair pattern of the forehead, linear skin lesions on the forehead, short palpebral fissures, a small skin tag on the right cheek, cone‐shaped teeth, and pectus carinatum. Dermatoglyphic studies documented aberrant distal palmar creases (simian crease variant), 8 arches, and reduced total finger ridge count. When serial photographs were reviewed, his facial characteristics became more obvious with increasing age. © 1995 Wiley‐Liss, Inc.
F‐syndrome (F‐form of acro‐pectoro‐vertebral dysplasia): Report on a second family
Authors: Camera Gianni , Camera Andrea , Pozzolo Silvano , Costa Margherita , Mantero Renzo 
Published: June 2005

AbstractWe report on a father and daughter in the second known family affected with F‐syn‐drome. The first family, with 8 affected members, was reported by Grosse et al. [1969: BD:OAS V (3):48–63]. F‐syndrome, an autoso‐mal‐dominant trait, is mainly characterized by acral defects that may also involve the sternum and the lumbosacral spine. Synostoses between capitate and hamate, and between talus and navicular, are invariably present; other carpal and tarsal bones are sometimes incorporated into the fusion. The hand malformation is principally a malformation of the first 2 rays. In our patients, the short and malformed thumb was webbed with the index finger, which was radially deviated with duplication of the middle and distal phalanges. In the feet, polydactyly and severe metatarsal and toe anomalies were present. The father had a prominent sternum with pectus excavatum, whereas the daughter had no sternal deformity. Both of them had a mild failure of fusion of posterior arch L5 and/Or Si. © 1995 Wiley‐Liss, Inc.
Multiple herniae: A defect in the celomic mesoderm?
Authors: Zaglul Horacio F. , Odita John C. 
Published: June 2005

AbstractWe report on a child with congenital bilateral cervical lung herniation with associated retrosternal (Morgagni), posterolateral (Bochdalek), esophageal hiatal, and inguinal herniae, and with multiple urinary bladder diverticuli. These multiple herniations may be secondary to a defect in the embryonic celomic mesoderm. © 1995 Wiley‐Liss, Inc.
Distinct skeletal abnormalities in four girls with Shprintzen‐Goldberg syndrome
Authors: Adés Lesley C. , Morris Lloyd L. , Power Rick G. , Wilson Meredith , Haan Eric A. , Bateman John F. , Milewicz Dianna M. , Sillence David O. 
Published: June 2005

AbstractWe describe 4 girls with Shprintzen‐Goldberg syndrome. Skeletal abnormalities common to 3 of them include bowing of long bones (with a variable degree of progression over time), flare of the metaphyses, a large anterior fontanel with persistent patency into the second to fourth years of life, 13 pairs of ribs, distinct vertebral abnormalities which were absent neonatally but evolved by the second year of life, and progressive osteopenia. These abnormalities were generalized and, in one case, progressive over the first few years of life. Communicating hydrocephalus was present in all 4 cases. The eldest, an 11‐year‐old girl, had additional anomalies not reported previously in this syndrome, including intestinal malrotation, an anteriorly placed anus, and mild cerebral atrophy. This is the first detailed report of skeletal manifestations in this rare disorder of unknown cause. These cases, in conjunction with a review of the literature, suggest that skeletal abnormalities are common in Shprintzen‐Goldberg syndrome. © 1995 Wiley‐Liss, Inc.
Mutations in PAX3 that cause Waardenburg syndrome type I: Ten new mutations and review of the literature
Authors: Baldwin Clinton T. , Hoth Christopher F. , Macina Roberto A. , Milunsky Aubrey 
Published: June 2005

AbstractWaardenburg syndrome (WS) is an autosomal‐dominant disorder characterized by sensorineural hearing loss, dystopia canthorum, and pigmentary disturbances, and it represents the most common form of inherited deafness in infants. WS type I is characterized by the presence of dystopia canthorum, while individuals with WS type II have normally‐located canthi. WS type III is similar to WS type I but is also characterized by musculoskeletal abnormalities. Defects in the PAX3 gene, a transcription factor expressed during embryonic development, have been shown to cause WS types I and III in several families. In contrast, mutations in PAX3 do not cause WS type II, and linkage of the disease to other chromosomal regions has been demonstrated. We describe 10 additional mutations in the PAX3 gene in families with WS type I. Eight of these mutations are in the region of PAX3, where only one mutation has been previously described. These mutations, together with those previously reported, cover essentially the entire PAX3 gene and represent a wide spectrum of mutations that can cause WS type I. Thus far, all but one of the mutations are private; only one mutation has been reported in two apparently unrelated families. Our analysis thus far demonstrates little correlation between genotype and phenotype; deletions of the entire PAX3 gene result in phenotypes indistinguishable from those associated with single‐base substitutions in the paired domain or homeodomain of PAX3. Moreover, two similar mutations in close proximity can result in significantly different phenotypes, WS type I in one family and WS type III in another. © 1995 Wiley‐Liss, Inc.
Acute intermittent porphyria: A single‐base deletion and a nonsense mutation in the human hydroxymethylbilane synthase gene, predicting truncations of the enzyme polypeptide
Authors: Lee Grace Y. , Astrin Kenneth H. , Desnick Robert J. 
Published: June 2005

AbstractAcute intermittent porphyria (AIP) is an autosomal‐dominant inborn error of metabolism that results from the half‐normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase (HMB‐synthase). AIP is an ecogenetic condition, since the life‐threatening acute attacks are precipitated by various factors, including drugs, alcohol, fasting, and certain hormones. Biochemical diagnosis is problematic, and the identification of mutations in the HMB‐synthase gene provides accurate detection of presymptomatic heterozygotes, permitting avoidance of the acute precipitating factors. By direct solidphase sequencing, two mutations causing AIP were identified, an adenine deletion at position 629 in exon 11(629delA), which alters the reading frame and predicts premature truncation of the enzyme protein after amino acid 255, and a nonsense mutation in exon 12 (R225X). These mutations were confirmed by either restriction enzyme analysis or family studies of symptomatic patients, permitting accurate presymptomatic diagnosis of affected relatives. © 1995 Wiley‐Liss, Inc.
Geleophysic dysplasia: A report of three affected boys—prenatal ultrasound does not detect recurrence
Authors: Rosser Elisabeth M. , Wilkinson Andrew R. , Hurst Jane A. , McGaughran Julie M. , Donnai Dian 
Published: June 2005

AbstractGeleophysic dysplasia is characterized by short stature with short limbs and brachydactyly, a “happy” facial appearance, and joint contractures. Infiltration of heart valves and liver with a mucopolysaccharide‐like substance has been demonstrated in some patients. A metabolic pathogenesis is suspected, but has not yet been identified. We report on 3 boys with the condition, 2 of whom are brothers. Serial ultrasound scans were performed on 2 of the cases during pregnancy, but short limbs did not become obvious until after 28 weeks of gestation, making it an uninformative procedure for prenatal diagnosis. © 1995 Wiley‐Liss, Inc.
Absence of correlation between utrophin localization and quantity and the clinical severity in Duchenne/Becker dystrophies
Authors: Vainzof Mariz , Passos‐Bueno Maria Rita , Man Nguyen Thi , Zatz Mayana 
Published: June 2005

AbstractWhile present in the surface membrane of embryonic muscle fibers, in adult normal muscle fibers, utrophin is restricted to the motor endplate and cell of blood vessel walls. However, the observation that utrophin is maintained in the extrajunctional plasma membrane in Duchenne (DMD) and in mdx muscle fibers has led to the suggestion that excess utrophin might compensate for dystrophin deficiency in the Xp21 muscular dystrophies. In order to detect an inverse correlation of utrophin presence and clinical severity, we have assessed utrophin distribution and quantity in DMD and Becker (BMD) patients of different ages and stages of clinical severity. All patients showed a positive discontinuous immunolabeling of utrophin on the sarcolemma, staining equally small and large muscle fibers, indicating that immature characteristics are maintained in such fibers. On Western blot, utrophin bands with concentrations 2‐ to 10‐fold greater than in normal controls were detected in all DMD/BMD patients. However, no negative correlation was found between the amount of utrophin and the severity of clinical course, implying that the detectable utrophin levels in these patients did not compensate for dystrophin deficiency. In a DMD patient with growth hormone (GH) deficiency and a BMD‐like clinical course, utrophin levels were comparable to the other typical DMD cases, which reinforces the hypothesis that the observed increase in utrophin is apparently not responsible for a milder clinical course in some patients with Xp21 muscular dystrophies. © 1995 Wiley‐Liss, Inc.
Reduced fecundity in male ALS gene‐carriers
Authors: Johnson W. G. , Lucek P. R. , Chatkupt S. , Furman Y. , Lustenberger A. , Lazzarini A. 
Published: June 2005

AbstractIn order to study genetic aspects in multicase families, 89 amyotrophic lateral sclerosis (ALS) and 214 Parkinson disease (PD) kindreds were analyzed in parallel studies. Obligate gene‐carriers were identified as described previously [Chatkupt et al., 1992: Am J Med Genet 44:508–512]. There were fewer children per gene‐carrier male (2.42) than per gene‐carrier female (3.25, Student's t‐test, P <.0003) for ALS but not for other diseases. The data taken together suggest that fecundity in ALS gene‐carriers was reduced in males, possibly as a result of reduced fertility. Since childbearing is usually accomplished well before the onset of neurological symptoms in ALS, and since reduced fecundity was found in male ALS gene‐carriers, these findings raise the possibility that an ALS gene might have a pleiotrophic effect on fertility in males occurring decades before the onset of neurological symptoms. Evidence is presented linking reactive oxygen species to reduced fertility in males. Alternatively, decreased or nonfunctional androgen receptors could play a role. © 1995 Wiley‐Liss, Inc.