bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canavan disease: Carrier‐frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay
Authors: Feigenbaum Annette , Moore Robert , Clarke Joe , Hewson Stacy , Chitayat David , Ray Peter N. , Stockley Tracy L. 
Published: December 2003

AbstractCanavan disease (CD) is an autosomal recessive progressive neurodegenerative disorder prevalent in the Ashkenazi Jewish (AJ) population. The carrier rate for the most common mutations that cause CD in the AJ population is often quoted as 1:37–1:40. This is not supported by our finding of only two diagnosed cases of CD in the last 20 years in the Toronto AJ population of 160,000 and an estimated birth rate of 1,500–2,000 per year. Therefore, we embarked on a prevalence cross‐sectional screening study to determine the carrier rate of CD in this population. In order to perform low‐cost, high‐throughput population testing for CD using molecular techniques, we first developed a novel molecular assay using multiplex fluorescent allele specific polymerase chain reaction (PCR) to test for the three most common mutations causing CD in the AJ population (A854C, C693A, C914A) and a neutral polymorphism at the site of the C693A mutation. During testing it was noted that individuals who were carriers of the A854C mutation also had a T polymorphism at the site of the C693A mutation (Y231X). We confirmed that in all A854C carriers the 854C mutation was in disequilibrium with the 693T polymorphism, indicating a founder chromosome for the A854C mutation in the AJ population. Twenty‐five carriers were found from 1,423 samples yielding a carrier rate of 1:57, differing from the widely quoted frequency of 1:40 and supporting our observed frequency of disease. © 2003 Wiley‐Liss, Inc.
Immunohistochemical FMRP studies in a full mutated female fetus
Authors: Rifé M. , Nadal A. , Milà M. , Willemsen R. 
Published: December 2003

AbstractFragile X syndrome (FXS) is the most common form of inherited mental retardation. Clinical manifestations are due to the absence of the FMRP protein. Affected patients have widely variable phenotypes which are more variable in females than males, presumable due to X inactivation. We report the expression pattern of FMRP in cerebral cortex and ovary in a control and a full‐mutated female fetus. FMRP was expressed in mutated and control fetal tissues, although at different levels and patterns. Control fetal cerebral cortex showed FMRP expression in almost all cells, whereas the full mutation carrier showed FMRP positivity in roughly 50% of cortical cells without any specific pattern. In the ovary samples, FMRP expression was seen in all germ cells surrounded by FMRP‐negative paragranulosa and interstitial cells. The Müllerian epithelium of the fetal Fallopian tube was continuously positive in the control case, whereas the full mutation carrier showed a discontinuous patchy pattern. Expression of homologue proteins FXR1P and FXR2P showed no differences between control and full mutation fetuses. The pattern of FMRP expression in full mutation carrier females is in agreement with a random X‐inactivation in maturing fetal tissues. Immunohistochemical results on cerebral tissues provide a clue for the variation of mental affection among female carriers, depending not only on the number of cells devoid of FMRP, but also on the ultimate destination of those cells in sensitive or more silent location for a proper cerebral development. © 2003 Wiley‐Liss, Inc.
Results of a genome‐wide linkage scan for stuttering
Authors: Shugart Yin Yao , Mundorff Jennifer , Kilshaw James , Doheny Kimberly , Doan Betty , Wanyee Jacqueline , Green Eric D. , Drayna Dennis 
Published: December 2003

AbstractWe performed a linkage study of stuttering using 392 markers distributed across the genome in a series of 68 families identified in the general outbred population of North America and Europe. Standardized diagnosis was performed using recorded samples of both conversation and reading, in which stuttering dysfluencies were scored as percentage of dysfluent words and syllables. Analysis was first performed using non‐parametric methods implemented in GENEHUNTER, where we obtained maximum statistical support for markers of chromosome 18, with a maximum NPL (Sall) of 1.51 at D18S976. The single largest pedigree within our sample (pedigree 0006) alone gave an NPL of 4.72 at D18S976. For fine mapping, we analyzed 18 markers on chromosome 18 across all families using ALLEGRO. Overall NPL (Srobdom) scores >5 were obtained with markers on 18p, and Zlr scores ≥2.5 on 18p and proximal 18q. Furthermore, pedigree 0006 alone gave an NPL (Srobdom) of 5.35. Overall our results suggest chromosome 18 may harbor a predisposing locus for this disorder, and additional genes may exist. Published 2003 Wiley‐Liss, Inc.
The 10q24‐linked split hand/split foot syndrome (SHFM3): Narrowing of the critical region and confirmation of the clinical phenotype
Authors: Roscioli Tony , Taylor Peter J. , Bohlken Andrew , Donald Jennifer A. , Masel John , Glass Ian A. , Buckley Michael F. 
Published: December 2003

AbstractIn this communication we describe the clinical and molecular genetic findings in a family with a variable ectrodactyly linked to SHFM3. This is only the second detailed report of the clinical features of the SHFM3 linked syndrome in a large pedigree. Within this family the expressivity of the condition ranges from the classical ectrodactyly deformity to partial absence of the thumb and agenesis of the distal tip of the index finger. There is discordant limb severity, with the feet more severely affected than the hands. Two individuals have a nail dysplasia indicating the presence of a minor ectodermal component. A cleft palate was present in one individual. Radiological features of family members include short metacarpals with rounded proximal heads, agenesis of the radial ray, epiphysial coning, and an unusual supernumerary ossicle opposed to the distal phalanx of the left thumb. Genetic mapping studies in this family exclude p63 involvement and demonstrate that ectrodactyly in this pedigree is linked to the SHFM3 region on chromosome 10q24. A meiotic recombination event enabled exclusion of a maximum of 1.9 Mb of DNA from the previously known critical region thereby narrowing the critical interval to between D10S1265 and D10S222, with the minimal critical region being between D10S1240 and D10S1267. Further investigations are in progress to identify the gene within the SHFM3 critical region responsible for ectrodactyly. © 2003 Wiley‐Liss, Inc.
A girl with duplication 17p10‐p12 associated with a dicentric chromosome
Authors: Shaw Christine J. , Stankiewicz Pawel , Christodoulou John , Smith Ellie , Jones Kristi , Lupski James R. 
Published: December 2003

AbstractWe report a 7½‐year‐old girl with an ∼9.5 Mb duplication of proximal 17p. Her clinical features include moderately severe developmental delay, absence of speech, talipes, congenital dislocation of the hips, premature adrenarche, dysmorphic facial features, deep palmar creases, and signs and symptoms of peripheral neuropathy consistent with Charcot–Marie–Tooth disease type 1A (CMT1A). Chromosome analysis revealed a partially duplicated 17p with two centromeres on the derivative chromosome. Fluorescence in situ hybridization (FISH) analysis demonstrated the tandemly duplicated segment spans 17p10‐p12, including the entire Smith–Magenis syndrome (SMS) critical region and a portion of the CMT1A critical region. One breakpoint mapped within the centromere and the second breakpoint mapped within the CMT1A critical region, distal to the PMP22 gene. Microsatellite polymorphism studies showed that the duplicated chromosome is of maternal origin. We compare the clinical features of our patient to those of individuals with partial trisomy of proximal 17p to further delineate the genotype–phenotype correlation associated with segmental duplication of this chromosomal region. © 2003 Wiley‐Liss, Inc.
A case of Costello with parathyroid adenoma and hyperprolactinemia
Authors: Cakir Mehtap , Arici Cumhur , Tacoy Sukran , Karayalcin Umit 
Published: December 2003

AbstractA 23‐year‐old female with Costello syndrome is presented. She had mental retardation, macrocephalia, “coarse” facial features, deep palmar and plantar creases, hyperkeratosis in palms and soles, hyperpigmentation, curly hair, and cutis laxa, which are among the diagnostic features of the syndrome, and a history of hyperprolactinemia since the age of 16. Her present complaint was weakness and widespread bone‐pain. In routine biochemistry, she had an elevated calcium level of 11.1 (8.6–10.2) mg/dl and her DEXA evaluation was consistent with osteoporosis (vertebra and femur T score <−2.5). High PTH levels, 103 (8–78) pg/ml, suggested presence of a parathyroid adenoma. Tc‐MIBI scintigraphy revealed two focuses of pathological uptake, one located inferior to left lobe of thyroid and the other in the superior left lobe of thyroid gland. After parathyroid adenomectomy, her serum calcium and PTH levels returned to normal values. This is the first case of parathyroid adenoma and hyperprolactinemia in the literature, reported in a patient with Costello syndrome. © 2003 Wiley‐Liss, Inc.
Interstitial deletion 9q22.32‐q33.2 associated with additional familial translocation t(9;17)(q34.11;p11.2) in a patient with Gorlin–Goltz syndrome and features of Nail‐Patella syndrome
Authors: Midro Alina T. , Panasiuk Barbara , Tümer Zeynep , Stankiewicz Paweł , Silahtaroglu Asli , Lupski James R. , Zemanova Zuzana , Stasiewicz‐Jarocka Beata , Hubert Ewa , Tarasów Eugeniusz , Famulski Waldemar , Zadrożna‐Tołwińska Barbara , Wasilewska Ewa , Kirchhoff Marie , Kalscheuer Vera , Michalova Kyra , Tommerup Niels 
Published: December 2003

AbstractThe phenotype of Gorlin–Goltz syndrome or basal cell nevus syndrome (BCNS, #109400, OMIM), a Mendelian trait due to PTCH mutations has been reported in a few cases of interstitial deletion of chromosome 9q. We present an 11‐year‐old girl with clinical features consistent with BCNS including bridging of sella turcica, biparietal bossing, downward slanting palpebral fissures, mandible prognathism, pectus excavatum, thumb abnormalities, occult spina bifida at L5‐S4, numerous basal cell nevi, and single basal cell carcinoma. Cytogenetic analysis using high‐resolution banding techniques and fluorescence in situ hybridization (FISH) revealed interstitial chromosome deletion 9q22.32‐q33.2 involving the PTCH gene as a secondary breakage event to a chromosome translocation t(9;17)(q34.1;p11.2)mat. Further FISH studies showed the translocation breakpoint on 9q34.11 maps proximal to ABL, between the BAC clone RP11‐88G17 and the LMX1B gene. The latter gene encodes a transcription factor, in which loss of function mutations are responsible for the nail‐patella syndrome (NPS, #161200 OMIM). Interestingly, some features of our proband (e.g., bilateral patellar dysplasia and abnormal clavicular shape), as well as her healthy sister who carries the same translocation, are also found in patients with NPS. The chromosome 17p11.2 breakpoint maps in the Smith‐Magenis syndrome common deletion region, within two overlapping BAC clones, CTD‐2354J3 and RP11‐311F12. © 2003 Wiley‐Liss, Inc.
Unexpected death and critical illness in Prader–Willi syndrome: Report of ten individuals
Authors: Stevenson David A. , Anaya Theresa M. , Clayton‐Smith Jill , Hall Bryan D. , Van Allen Margot I. , Zori Roberto T. , Zackai Elaine H. , Frank Gary , Clericuzio Carol L. 
Published: December 2003

AbstractIndividuals with Prader–Willi syndrome (PWS) generally survive into adulthood. Common causes of death are obesity related cor pulmonale and respiratory failure. We report on a case series of eight children and two adults with unexpected death or critical illness. Our data show age‐specific characteristics of PWS patients with fatal or life‐threatening illnesses. Under the age of 2 years, childhood illnesses in general were associated with high fever and rapid demise or near‐demise. Hypothalamic dysfunction likely plays a role in exaggerated fever response, but also perhaps in central regulation of adrenal function. Below average sized adrenal glands were found in three children, which raises the possibility of unrecognized adrenal insufficiency in a subset of individuals with PWS and emphasizes the vital role of autopsy. The tub drowning death of an adult patient could be related to central hypersomnia, which has been reported in PWS. We suggest that increased risk for critical illness be considered in the discussion of anticipatory guidance for the care of infants with PWS. Since a number of children died while hospitalized, particularly close observation of PWS children who are ill enough to warrant hospital admission is recommended. © 2003 Wiley‐Liss, Inc.
New syndrome: Focal dermal hypoplasia, morning glory anomaly, and polymicrogyria
Authors: Giampietro Philip F. , Babu Deepti , Koehn Monica A. , Jacobson Daniel M. , Mueller‐Schrader Karla A. , Moretti Cara , Patten Stella F. , Shaffer Lisa G. , Gorlin Robert J. , Dobyns William B. 
Published: December 2003

AbstractRegional skin hypoplasia has been described in several genetic syndromes, including focal dermal hypoplasia (FDH), microphthalmia with linear skin defects (MLS), oculocerebrocutaneous syndrome (OCCS), and terminal osseous dysplasia and pigmentary defects (TODP). All but OCCS have been reported to follow an X‐linked inheritance pattern. We describe a 14‐year‐old girl with clinical features overlapping with these disorders. She had mild mental retardation, macrocephaly, microphthalmia, right‐sided morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly. A swirling pattern of skin hypopigmentation, papular hypopigmented and herniated skin lesions reminiscent of FDH most prominent over her face, head, hands, and feet was evident. Brain magnetic resonance imaging (MRI) showed polymicrogyria (most severely in the perisylvian and mesial frontal regions), enlarged left lateral ventricle, partial agenesis of the corpus callosum, and optic nerve tumor on the right. Dermatopathologic examination of the skin lesions was consistent with basaloid follicular hamartomas. The skin and digit anomalies observed overlap with FDH, but polymicrogyria, basaloid follicular hamartomas, optic nerve tumor, and morning glory anomaly have not previously been described in FDH. Skin defects in MLS are linear and the eyes typically have sclerocornea. Polymicrogyria has been described in OCCS, but not in any of the other three syndromes. The limb anomalies in TODP are reductions rather than polysyndactyly. Skin defects are localized to the face, and digital fibromas usually occur. While significant overlap exists between all four of the syndromes discussed, we believe that the constellation of anomalies observed in this girl most likely comprises a newly recognized syndrome. © 2003 Wiley‐Liss, Inc.
Longterm follow‐up in chondrodysplasia punctata, tibia–metacarpal type, demonstrating natural history
Authors: Savarirayan Ravi , Boyle Robert J. , Masel John , Rogers John G. , Sheffield Leslie J. 
Published: December 2003

AbstractWe report the longterm clinical and radiological progression in three unrelated patients with the tibia–metacarpal form of chondrodysplasia punctata (CDP‐TM). The patients were followed for 37, 25, and 32 years, respectively. At follow‐up intellectual function was normal, and physical function was well preserved. There was also marked resolution of several significant early radiographic features. The patients attained adult heights of 152, 138, and 148 cm. Two patients had chronic serous otitis media requiring tympanostomy tubes during childhood. One patient suffered persisting back pain related to spinal stenosis and required lumbar laminectomy at the age of 26 years. One patient had hip dysplasia requiring orthopedic surgical intervention. All patients had recurrent patella dislocation. Sterol and very long chain fatty acid profiles, FISH analysis for SHOX gene deletions, blood lymphocyte karyotype, and phytanic acid levels were normal in those tested, and no mutations in arylsulfatase D and E genes were detected. These data suggest that the longterm clinical and functional prognosis in this condition appears to be better than that expected based on initial clinical and radiological findings. © 2003 Wiley‐Liss, Inc.
Hepatic fibrosis in Kabuki syndrome
Authors: Nobili Valerio , Marcellini Matilde , Devito Rita , Capolino Rossella , Viola Laura , Digilio M. Cristina 
Published: December 2003

AbstractKabuki (Niikawa–Kuroki) syndrome (KS) is characterized by a distinctive face, mental retardation, growth deficiency, skeletal anomalies, dermatoglyphic abnormalities, palatal anomalies, congenital heart defects, and urogenital malformations. Congenital hepatic abnormalities have been sporadically described in patients with KS from the literature, consisting of extrahepatic biliary atresia, neonatal sclerosing cholangitis, and severe neonatal jaundice. We report here on an additional patient with a congenital abnormality of the liver consisting of hepatic fibrosis. To our knowledge, idiopathic congenital hepatic fibrosis has not been reported in KS. Thus, our observation expands the spectrum of liver malformations found in KS with the inclusion of hepatic fibrosis and supports the evidence that hepatic abnormalities may not be uncommon in KS. Clinician should be advised to search for the specific facial anomalies of KS in patients with syndromic congenital hepatic diseases, and KS should be added to the list of previously recognized multiple congenital anomaly syndromes with hepatic involvement. Due to the frequent association with congenital heart malformations, KS should be considered in the evaluation of patients with neonatal liver disease and cardiac malformation. Due to the expression patterns of Notch genes, involvement of the Notch signaling pathway in the development of heart and liver anomalies in KS should be considered. © 2003 Wiley‐Liss, Inc.
1,1‐allylboration of bis(silyl)ethynes: electron‐deficient SiHB bridges and novel heterocycles via intramolecular hydrosilylation
Authors: Wrackmeyer Bernd , Tok Oleg L. , Bubnov Yuri N. 
Published: December 2003

AbstractThe reaction of bis(silyl)ethynes 2–4, bearing one, two and three hydrides at one of the silicon atoms, with triallylborane 1 leads primarily to alkenes 5, 8 and 11 respectively by 1,1‐allylboration. In these alkenes, the diallylboryl and the silyl group bearing one or more SiH functions are in cis‐positions at the CC bond, giving rise to the formation of an electron‐deficient SiHB bridge. This follows unambiguously from the consistent set of NMR data, in particular from the observation of isotope‐induced chemical shifts 2Δ10/11B(29Si). The activation of the SiH bond in 5, 8 and 11 induces intramolecular hydrosilylation under very mild reaction conditions to give 1,4‐silabora‐cyclo‐2‐heptenes 7, 10 and 13 respectively. Upon heating, these seven‐membered heterocycles undergo ring contraction by 1,1‐deallylboration to give the 1‐sila‐cyclo‐2‐hexenes 14–16, and bear an exocyclic diallylboryl group in 3‐position. All proposed structures are based on consistent 1H, 11B, 13C and 29SiNMR data. Copyright © 2004 John Wiley & Sons, Ltd.
Smooth muscle stem cells
Authors: Hirschi Karen K. , Majesky Mark W. 
Published: December 2003

AbstractVascular smooth muscle cells (SMCs) originate from multiple types of progenitor cells. In the embryo, the most well studied SMC progenitor is the cardiac neural crest stem cell. Smooth muscle differentiation in the neural crest lineage is controlled by a combination of cell intrinsic factors, including Pax3, Tbx1, FoxC1, and serum response factor, interacting with various extrinsic factors in the local environment such as bone morphogenetic proteins (BMPs), Wnts, endothelin (ET)‐1, and FGF8. Additional sources of multipotential cells that give rise to vascular SMCs in the embryo include proepicardial cells and possibly endothelial progenitor cells. In the adult, vascular SMCs must continually repair arterial injuries and maintain functional mass in response to changing demands upon the vessel wall. Recent evidence suggests that this is accomplished, in part, by recruiting multipotential vascular progenitors from bone marrow‐derived stem cells as well as from less well defined sources within adult tissues themselves. This article will review our current understanding of the origins of vascular SMCs from multipotential stem and progenitor cells in developing as well as adult vasculature. Anat Rec Part A 276A:22–33, 2004. © 2004 Wiley‐Liss, Inc.
The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells
Authors: Wessels A. , Pérez‐Pomares J.M. 
Published: December 2003

AbstractAfter its initial formation the epicardium forms the outermost cell layer of the heart. As a result of an epithelial‐to‐mesenchymal transformation (EMT) individual cells delaminate from this primitive epicardial epithelium and migrate into the subepicardial space (Pérez‐Pomares et al., Dev Dyn 1997; 210:96–105; Histochem J 1998a;30:627–634). Several studies have demonstrated that these epicardially derived cells (EPDCs) subsequently invade myocardial and valvuloseptal tissues (Mikawa and Fischman, Proc Natl Acad Sci USA 1992;89:9504–9508; Mikawa and Gourdie, Dev Biol 1996;174:221–232; Dettman et al., Dev Biol 1998;193:169–181; Gittenberger de Groot et al., Circ Res 1998;82:1043–1052; Manner, Anat Rec 1999;255:212–226; Pérez‐Pomares et al., Dev. Biol. 2002b;247:307–326). A subset of EPDCs continue to differentiate in a variety of different cell types (including coronary endothelium, coronary smooth muscle cells (CoSMCs), interstitial fibroblasts, and atrioventricular cushion mesenchymal cells), whereas other EPDCs remain in a more or less undifferentiated state. Based on its specific characteristics, we consider the EPDC as the ultimate ‘cardiac stem cell’. In this review we briefly summarize what is known about events that relate to EPDC development and differentiation while at the same time identifying some of the directions where EPDC‐related research might lead us in the near future. Anat Rec Part A 276A:43–57, 2004. © 2004 Wiley‐Liss, Inc.
Stem cells and the formation of the myocardium in the vertebrate embryo
Authors: Eisenberg Leonard M. , Kubalak Steven W. , Eisenberg Carol A. 
Published: December 2003

AbstractA major goal in cardiovascular biology is to repair diseased or damaged hearts with newly generated myocardial tissue. Stem cells offer a potential source of replacement myocytes for restoring cardiac function. Yet little is known about the nature of the cells that are able to generate myocardium and the conditions they require to form heart tissue. A source of information that may be pertinent to addressing these issues is the study of how the myocardium arises from progenitor cells in the early vertebrate embryo. Accordingly, this review will examine the initial events of cardiac developmental biology for insights into the identity and characteristics of the stem cells that can be used to generate myocardial tissue for therapeutic purposes. Anat Rec Part A 276A:2–12, 2004. © 2004 Wiley‐Liss, Inc.