bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homozygosity for a novel splice site mutation in the cardiac myosin‐binding protein C gene causes severe neonatal hypertrophic cardiomyopathy
Authors: Xin Baozhong , Puffenberger Erik , Tumbush John , Bockoven J.R. , Wang Heng 
Published: October 2007

AbstractHypertrophic cardiomyopathy is typically inherited in an autosomal dominant pattern and has a variable age of onset and prognosis. Mutations in the myosin‐binding protein C (MYBPC3) gene are one of the most frequent genetic causes of the disease. Patients with MYBPC3 mutations generally have a late onset and a relatively good prognosis. We report here more than 20 Old Order Amish children with severe neonatal hypertrophic cardiomyopathy caused by a novel homozygous splice site mutation in the MYBPC3 gene. The affected children typically presented with signs and symptoms of congestive heart failure during the first 3 weeks of life. Echocardiography revealed hypertrophic non‐obstructive cardiomyopathy. These children had a life span averaging 3–4 months. All patients died from heart failure before 1 year of age unless they received a heart transplant. A genome‐wide mapping study was performed in three patients. The disease related gene was localized to a 4.6 Mb region on chromosome 11p11.2‐p11.12. This homozygous block contained MYBPC3, a previously identified cardiomyopathy related gene. We identified a novel homozygous mutation, c.3330 + 2T > G, in the splice‐donor site of MYBPC3 intron 30. The mutation resulted in skipping of the 140‐bp exon 30, which led to a frame shift and premature stop codon in exon 31 (p.Asp1064GlyfsX38). We have found a substantial incidence of this phenotype in Old Order Amish communities. It is also concerning that many unidentified heterozygous individuals who are at risk for development of hypertrophic cardiomyopathy do not receive proper medical attention in the communities. © 2007 Wiley‐Liss, Inc.
Small supernumerary chromosome marker generating complete and pure trisomy 18p, characterized by molecular cytogenetic techniques and review
Authors: Rodríguez L. , Liehr T. , Mrasek K. , Mansilla E. , Martínez‐Fernández M.L. , Garcia A. , Martínez‐Frías M.L. 
Published: October 2007

AbstractSmall supernumerary marker chromosomes (sSMC) have been described from all human chromosomes with different sizes and shapes. However, it is difficult to know the clinical manifestations associated with them, because such knowledge depends on the size, presence of euchromatic material, degree of mosaicism and/or uniparental disomy (UPD). Pure trisomy of the whole arm of chromosome 18 (18p), has been described in only a few cases and the general consensus is that there is a mild phenotypic effect. Here we report on a newborn male presenting with an atrial septal defect and a club foot. The high resolution G‐band karyotype (550–850 bands) and the molecular cytogenetic techniques revealed in all cells the presence of an sSMC, which was a complex derivative from the short arm of a chromosome 18 (18p) and a centromere of a chromosome 13/21. His healthy mother had the same sSMC in all analyzed cells. With the present case, we support the previous suggestion that this unusual chromosome trisomy 18p has little clinical repercussions. © 2007 Wiley‐Liss, Inc.
Genotype/phenotype correlations in two patients with 12q subtelomere deletions
Authors: Niyazov Dmitriy M. , Nawaz Zafar , Justice April N. , Toriello Helga V. , Martin Christa Lese , Adam Margaret P. 
Published: October 2007

AbstractSubtelomeric imbalances have been implicated in developmental delay and mental retardation (MR) and described for most chromosomes. This study reports the first detailed description of two individuals with de novo 12q subtelomere deletions and high‐resolution mapping of their deletion size with oligonucleotide array CGH for genotype/phenotype comparisons. Patient 1 is an 8‐year‐old male with borderline mild MR, food‐seeking behavior, obesity, no significant dysmorphic facial features, abnormal hair whorl pattern, brachydactyly and mild clinodactyly. Patient 2 is a 12‐year‐old male with mild MR, food‐seeking behavior, obesity, short stature, mild dysmorphic facial features, multicystic kidney and unilateral cryptorchidism. Both patients share a deleted region of ∼1.6 Mb, including 14 known genes, which perhaps contributed to their similar phenotypes. However, Patient 2 has more severe MR and organ system involvement, possibly due to the larger deletion size (∼4.5 Mb) including an additional eight genes, although it is difficult to make phenotype/genotype correlations based on only two patients. Due to the relatively mild presentation of both of our patients, we propose that a proportion of individuals with subtelomeric imbalances may go undetected and therefore, recommend subtelomeric studies be carried out for cases of unexplained mild MR or isolated learning disability (LD) with behavioral problems in the absence of major dysmorphic features or birth defects. In addition, 12q subtelomeric deletions should be considered in the differential diagnosis of patients presenting with food‐seeking behavior and resultant obesity, as well as those referred to rule out Prader–Willi syndrome. © 2007 Wiley‐Liss, Inc.
van den Ende–Gupta syndrome: Laryngeal abnormalities in two siblings
Authors: Carr Christopher W. , Carron Jeffrey D. , Lachman Ralph S. , Abdul‐Rahman Omar A. 
Published: October 2007

AbstractIn 1992, van den Ende et al. first reported an autosomal recessive multiple congenital anomaly syndrome characterized by blepharophimosis, arachnodactyly, and congenital contractures in a Brazilian girl born to consanguineous parents. Since then, nine total patients have been reported with van den Ende–Gupta syndrome (VDEGS), and the syndrome's phenotype has been found to also include additional dysmorphic facial features, palatal abnormalities, and slender skeletal features. We present two African‐American sisters born to nonconsanguineous parents who have been diagnosed with VDEGS. Both sisters developed stridor and were found to have an unusual malformation characterized by large, globular cuneiform cartilages, shortened aryepiglottic folds, a tightly coiled epiglottis, and laryngomalacia. Both patients underwent supraglottoplasty with a successful outcome. A review of the literature reveals that airway problems have been reported in a previous patient. However, no specific airway anomaly has been reported. We suggest that all patients with VDEGS and stridor undergo direct laryngoscopy with consideration for surgical correction. © 2007 Wiley‐Liss, Inc.
Limb anomalies in patients with CHARGE syndrome: An expansion of the phenotype
Authors: Van de Laar Ingrid , Dooijes Dennis , Hoefsloot Lies , Simon Marleen , Hoogeboom Jeanette , Devriendt Koenraad 
Published: October 2007

AbstractCHARGE syndrome is characterized by a wide clinical variability. During the past years the phenotypic spectrum was markedly expanded. Limb anomalies were initially not recognized as part of the phenotype but more recently mild limb anomalies were described in approximately 30% of the patients. We report on three patients with several major features of CHARGE syndrome who, in addition, presented severe limb anomalies including monodactyly, tibia aplasia, and bifid femora. Three different heterozygous truncating mutations in the CHD7 gene were detected. It has been hypothesized before that the CHARGE syndrome is caused by a disruption of mesenchymal‐epithelial interaction. Given the expression of the CHD7 gene in the developing limb bud, it was anticipated that limb defects would belong to the spectrum of manifestations of CHARGE syndrome. The present observations provide further support to this hypothesis. © 2007 Wiley‐Liss, Inc.
Comparing phenotypes in patients with idiopathic autism to patients with velocardiofacial syndrome (22q11 DS) with and without autism
Authors: Kates Wendy R. , Antshel Kevin M. , Fremont Wanda P. , Shprintzen Robert J. , Strunge Leslie A. , Burnette Courtney P. , Higgins Anne Marie 
Published: October 2007

AbstractAt least three research groups have reported that autism is diagnosed in up to 20% of children with velocardiofacial syndrome (VCFS). However the degree of phenotypic overlap between VCFS‐affected children with autism and those with idiopathic autism has not been established. The purpose of this study was to define and differentiate the behavioral phenotype of autism in samples of children with either (VCFS) or idiopathic autism. Five groups of children ages 5–15 were included in the between‐group design. Parent report of autism behaviors (based on the Autism Diagnostic Interview‐Revised, ADI‐R) were compared between children with VCFS, children with VCFS and autism (VCFS + autism), siblings of the children with VCFS, a community control group, and a group of children with idiopathic autism. Autism diagnoses were based according to the ADI‐R. Parental responses to the ADI‐R indicated that relative to children with VCFS‐only, children with idiopathic autism and children with VCFS + autism exhibited less make believe play and more rituals, motor stereotypies and repetitive use of objects. However several other core autism behaviors, including difficulties sharing attention, deficits in gestural communication and initiating conversation, and presence of circumscribed interests, appear to be phenotypic VCFS behaviors, characterizing children with VCFS regardless of an autism diagnosis. Accordingly, the autism phenotype in VCFS differs to some extent from that of idiopathic autism. Several features of idiopathic autism are spared in VCFS, and other features appear to be a function of the VCFS phenotype independent of autism. These findings carry implications for clinicians who diagnose and treat VCFS or autism, and for researchers who study genotype–phenotype associations in autism. © 2007 Wiley‐Liss, Inc.
The emotional effects of genetic diseases: Implications for clinical genetics
Authors: McAllister Marion , Davies Linda , Payne Katherine , Nicholls Stuart , Donnai Dian , MacLeod Rhona 
Published: October 2007

AbstractThe aim of this qualitative study was to explore the emotional effects that may be common to many genetic conditions, or risk of genetic conditions, that could be appropriately targeted by clinical genetics services. The study sample comprised 52 individuals. Seven focus groups with patients of clinical genetics services, their representatives from patient support organizations and genetics healthcare providers were conducted. Focus groups were supplemented by 19 face‐to‐face interviews with patients and patient group representatives. Focus groups and interviews were audio taped, transcribed in full, and analyzed using the constant comparative method. Eight emotional effects of genetic diseases were identified: anxiety, worry about risks to children, guilt, anger, uncertainty, sadness and grief, depression, and redemptive adjustment. Two factors were identified that could modify the emotional effects; these were variability of genetic diseases, and lack of diagnosis/inappropriate care. Despite many negative effects of genetic disease being identified, results also suggest that redemptive adjustment is possible where a genetic condition is present in a family. Interventions designed to (1) adjust the modifying conditions and (2) help manage the emotional effects may facilitate adjustment and improve patient outcomes. © 2007 Wiley‐Liss, Inc.
Limb body wall complex and amniotic band sequence in sibs
Authors: Levy Ronaldo , Lacombe Didier , Rougier Yannick , Camus Erick 
Published: October 2007

AbstractWe report on a woman who gave birth consecutively to an infant with limb body wall complex (LBWC) and then to an infant with amniotic band sequence (ABS). This paper reviews the different etiological hypotheses and the classification problems for the amniotic band diseases. No maternal factors were found, but this clinical report suggests further research in this direction, as well as the need to look more closely at the relation between LBWC and ABS. © 2007 Wiley‐Liss, Inc.
Extensive molecular genetic analysis of the 3p14.3 region in patients with Zimmermann–Laband syndrome
Authors: Abo‐Dalo Benjamin , Kim Hyung‐Goo , Roes Melanie , Stefanova Margarita , Higgins Anne , Shen Yiping , Mundlos Stefan , Quade Bradley J. , Gusella James F. , Kutsche Kerstin 
Published: October 2007

AbstractZimmermann–Laband syndrome (ZLS) is a rare autosomal dominant inherited disorder characterized by a coarse facial appearance, gingival fibromatosis, and absence or hypoplasia of the terminal phalanges and nails of hands and feet. Additional, more variable features include hyperextensibility of joints, hepatosplenomegaly, mild hirsutism, and mental retardation. Mapping of the translocation breakpoints of t(3;8) and t(3;17) found in patients with the typical clinical features of ZLS defined a common breakpoint region of ∼280 kb located in 3p14.3, which includes the genes CACNA2D3 and WNT5A. Breakpoint cloning revealed that both translocations most likely occurred by non‐homologous (illegitimate) recombination. Mutation analysis of nine genes located in 3p21.1‐p14.3, including CACNA2D3, which is directly disrupted by one breakpoint of the t(3;17), identified no pathogenic mutation in eight sporadic patients with ZLS. Southern hybridization analysis and multiplex ligation‐dependent probe amplification (MLPA) did not detect submicroscopic deletion or duplication in either CACNA2D3 or WNT5A in ZLS‐affected individuals. Mutation analysis of nine conserved nongenic sequence elements (CNEs) in 3p21.1‐p14.3, which were identified by interspecies comparison and may represent putative regulatory elements for spatiotemporally correct expression of nearby genes, did not show any sequence alteration associated with ZLS. Taken together, the lack of a specific coding‐sequence lesion in the common region, defined by two translocation breakpoints, in sporadic patients with ZLS and an apparently normal karyotype suggests that either some other type of genetic defect in this vicinity or an alteration elsewhere in the genome could be responsible for ZLS. © 2007 Wiley‐Liss, Inc.
Association of the ENGRAILED 2 (EN2) gene with autism in Chinese Han population
Authors: Wang Lifang , Jia Meixiang , Yue Weihua , Tang Fulei , Qu Mei , Ruan Yan , Lu Tianlan , Zhang Handi , Yan Hao , Liu Jing , Guo Yanqing , Zhang Jishui , Yang Xiaoling , Zhang Dai 
Published: October 2007

AbstractHuman ENGRAILED 2 (EN2) gene is localized to 7q36, an autism susceptibility locus. En2 knockout mice display hypoplasia of cerebellum and a decrease in the number of Purkinje cell, which are similar to those reported for individuals with autism. Furthermore, deficits in social behavior were detected in En2−/− mice. Two recent studies have demonstrated that two intronic SNPs (rs1861972, rs1861973) in the EN2 gene are significantly associated with autism. To investigate whether this finding could be replicated in Chinese Han population, we performed the association study between eight single nucleotide polymorphisms (SNPs) of the EN2 gene and autism in 210 Chinese Han trios, using the family‐based association test (FBAT). The present study demonstrated that a preferential transmission of the rs3824068 A‐allele to affected offspring (A > G: Z = 2.399, P = 0.0165). After the Bonferroni correction, this statistical significance of preferential transmission did not remain. However, when haplotypes were constructed with multiple markers, a number of haplotypes including three two‐marker haplotypes, nine three‐marker haplotypes, one four‐marker haplotype, and one six‐marker haplotype, all of which contain the major allele A of rs3824068, displayed significantly associated with autism. These results were still significant after using the permutation method to obtain empirical P values. Thus, our data provide evidence that the EN2 gene may be implicated in the predisposition to autism in the Chinese Han population. © 2007 Wiley‐Liss, Inc.
EFHC2 SNP rs7055196 is not associated with fear recognition in 45,X Turner syndrome
Authors: Zinn Andrew R. , Kushner Harvey , Ross Judith L. 
Published: October 2007

AbstractThe neurocognitive phenotype of Turner syndrome (TS) includes deficits in social cognitive skills such as recognition of the facial affect expressing fear. A TS social cognition locus was previously mapped to a 5 megabase interval of Xp11.3‐p11.4 by Good et al. 2003. A recent study by these same workers found evidence for association of a SNP in the EFHC2 gene, rs7055196, within this interval with fear recognition in 45,X TS. As EFHC2 was not a biological candidate gene for this phenotype a priori, we sought to replicate their finding in an independent cohort of 45,X TS subjects, using the same instrument to measure facial affect fear recognition. In contrast to the previous results, we find no evidence of an association between rs7055196 genotype and fear recognition. Other variations in EFHC2 and other candidate genes should be tested for association with social cognition in 45,X TS. © 2007 Wiley‐Liss, Inc.
Association of dopamine, serotonin, and nicotinic gene polymorphisms with methylphenidate response in ADHD
Authors: Tharoor Hema , Lobos Elizabeth A. , Todd Richard D. , Reiersen Angela M. 
Published: October 2007

AbstractGene polymorphisms of the 3′ untranslated region (3′‐UTR) of the dopamine transporter (DAT1), Dopamine receptor exon 3 D4 variable number tandem repeat (DRD4VNTR), nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and serotonin transporter promoter (SLC6A4‐5HTTLPR) are under consideration as potential risk factors for attention‐deficit/hyperactivity disorder (ADHD). A post‐hoc attempt was made to investigate the association between the allelic variations of these candidate genes and retrospective parental report of response to methylphenidate in an ADHD‐enriched, population‐based twin sample. Subjects (N = 243) were selected from the twin sample based on parent report that the child had been treated with methylphenidate for ADHD symptoms. The functional polymorphisms screened were the VNTR located in the 3′‐UTR of the dopamine transporter, DRD4 VNTR, CHRNA4 (rs1044396 and rs6090384) and the long (LA and LG) and short (S) forms of the serotonin transporter promoter region. Logistic regression did not demonstrate a significant association between methylphenidate treatment response and the relevant polymorphisms. The sample size had high power to detect effect sizes similar to those reported in some prior methylphenidate pharmacogenetic studies; however, the categorical (yes/no) measure of parent‐reported treatment response may not have been sensitive enough to pick up statistically significant differences in treatment response based on genotype. Further studies including quantitative measures of treatment response are warranted. © 2007 Wiley‐Liss, Inc.
Changes in food processing and occlusal dental wear during the early agricultural period in northwest Mexico
Authors: Watson James T. 
Published: October 2007

AbstractCrown dimensions and occlusal surface wear rate and wear plane were evaluated using paired first and second mandibular molars from a sample of 84 Early Agricultural period (1600 B.C.–A.D. 200) skeletons from northwest Mexico. Although this period represents a major shift in subsistence strategies in the Sonoran Desert, from food‐foraging to agriculture, archaeological and dental pathology studies have identified this period as one of relative dietary stability. It was therefore predicted that very little variation in occlusal wear would have occurred between the early phase (San Pedro: 1600–800 B.C.) and late phase (Cienega: 800 B.C.–A.D. 200). Comparison of crown diameters identified some phenotypic differences between sexes but not between archaeological phases. Molar occlusal surfaces were then divided into four quadrants, and wear scores recorded for each quadrant. Principle axis analysis was performed between total wear scores of paired, adjacent first and second mandibular molars to assess rate and occlusal wear plane over time. The analysis demonstrated that both wear rate and wear plane increased from the early to the late phase of the Early Agricultural period. These results indicate that although diet may have indeed remained stable during this period in the Sonoran Desert increases in the rate of wear and wear plane may reflect changes in food‐processing techniques. It is suggested that more intensive processing of agricultural products during the Cienega phase simultaneously softened the diet to create more tooth‐contact wear and introduced more grit to cause faster and more angled wear on the molar occlusal surfaces. Am J Phys Anthropol, 2008. © 2007 Wiley‐Liss, Inc.
Biogeochemical and craniometric investigation of dietary ecology, niche separation, and taxonomy of Plio‐Pleistocene cercopithecoids from the Makapansgat Limeworks
Authors: Fourie Nicolaas H. , Lee‐Thorp Julia A. , Ackermann Rebecca Rogers 
Published: October 2007

AbstractThree sympatric fossil cercopithecoid genera (Cercopithecoides, Parapapio, and Theropithecus) occur in Members 3 and 4 at the Makapansgat Limeworks hominin locality, South Africa, and their presence in a single ecosystem suggest a certain degree of ecological and/or dietary differentiation between taxa. Here, we explore the extent of dietary niche separation amongst these taxa using stable isotope (13C/12C, 18O/16O) and trace‐element (Sr, Ba, Ca) analyses of fossil tooth enamel. In particular we searched for evidence of subtle niche separation between the more closely related, morphologically similar taxa of the genus Parapapio, as uncertainties exist around their taxonomy and taxonomic identification. Given these uncertainties, craniometric analyses were also performed to ground the dietary interpretations in a morphological context. The results found no clear taxonomic signal in the craniometric data for the Parapapio sample, and further indicate that this sample was no more variable morphologically than a single, geographically circumscribed, extant chacma baboon sample. In contrast, two overlapping dietary ecologies were found within this same Makapansgat Parapapio sample. Additionally, two widely differing dietary ecologies were found within the Cercopithecoides williamsi sample, while results for Theropithecus darti indicate a predominantly C4 diet. Hence, although biogeochemical dietary indicators point towards distinct dietary ecologies within and between fossil genera at Makapansgat, within the genus Parapapio disjunctions exist between the dietary categories and the taxonomic assignment of specimens. Am J Phys Anthropol, 2008. © 2007 Wiley‐Liss, Inc.
Clear polyurethane dispersions of nanometer size derived from carboxylic polycaprolactonediols
Authors: Lee Da‐Kong , Tsai Hong‐Bing , Tsai Ruey‐Shi 
Published: October 2007

AbstractAqueous polyurethanes dispersions of nanometer size derived from various carboxylic polycaprolactonediols of different molecular weights, carboxylic diols, including 2,2‐di(hydroxymethyl)propanoic acid (DMPA), 2,2‐di(hydroxymethyl)butanoic acid (DMBA), and di(4‐isocyanatocyclohexyl)methane (HMDI) were prepared by a method in which the dispersing procedure was modified to enhance the molecular weight. The molecular weight, particle size, and UV–vis spectra of the polyurethane dispersions were investigated. The tensile properties of the cast films were determined. The modified dispersing procedure gave polyurethane dispersions with higher molecular weight and better tensile strength. As the molecular weight of the carboxylic polycaprolactonediol decreases, the content of the ionic groups increases, the particle size decreases accordingly. As the molecular weight of the carboxylic polycaprolactonediol used is 1000 g/mol or below, the polyurethanes dispersions become completely clear. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008