bluuebunny/crossref_metadata_2025 huggingface dataset:
Dyggve–Melchior–Clausen syndrome and Smith–McCort dysplasia: Clinical and molecular findings in three families supporting genetic heterogeneity in Smith–McCort dysplasia
Authors: Neumann Luitgard M. , Ghouzzi Vincent El , Paupe Vincent , Weber Hans‐Peter , Fastnacht Elisabeth , Leenen Andreas , Lyding Sigrid , Klusmann Anne , Mayatepek Ertan , Pelz Jörg , Cormier‐Daire Valerie
Published: February 2006

Dyggve–Melchior–Clausen syndrome (DMC) (MIM 223800) and Smith–McCort dysplasia (SMC) (MIM 607326) are rare allelic autosomal recessive spondylo‐epi‐metaphyseal dysplasias (SEMDs) characterized by similar skeletal manifestations. Both phenotypes have been mapped to chromosome 18q21.1 and mutations in the DYM (dymeclin) gene were identified in 13 families with DMC and in two families with SMC. Most mutations identified in DMC predict a loss of function, while those identified in SMC are mainly missense mutations, presumably associated with residual DYM activity and a less severe phenotype. We studied three consanguineous families from Turkey, Lebanon, and Georgia, one with SMC and two with DMC and identified different homozygous DYM mutations (IVS3 194‐1G > A, 938_942delTGTCT) in the DMC families. No mutation was identified in the SMC family, possibly suggesting genetic heterogeneity of this disorder. © 2006 Wiley‐Liss, Inc.
Severe, fetal‐onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5?
Authors: Patel Millan S. , Becker Laurence E. , Toi Ants , Armstrong Dawna L. , Chitayat David
Published: February 2006

We present three siblings with a precise onset of fetal seizure‐like activity who had severe olivopontocerebellar hypoplasia (OPCH) and degeneration. Autopsies at 20, 27, and 37 weeks gestation showed diffuse central nervous system volume loss that was most marked for the cerebellum and brain stem structures. Neuropathological abnormalities included dysplastic, C‐shaped inferior olivary nuclei, absent or immature dentate nuclei, and cell paucity more marked for the cerebellar vermis than the hemispheres. Delayed development was seen in layer 2 of the cerebral cortex and in Purkinje cells of the cerebellum. Prenatal monitoring defined a developmental window of 16–18 weeks gestation when ultrasonic assessment of cerebellar width was used for prenatal diagnosis. We discuss our findings in the context of the differential diagnosis for infantile (O)PCH and propose a classification scheme for the pontocerebellar hypoplasias. These patients represent the earliest reported with OPCH and provide unique information regarding the developmental neuropathology of this condition. © 2006 Wiley‐Liss, Inc.
Minimal phenotype in a girl with trisomy 15q due to t(X;15)(q22.3;q11.2) translocation
Authors: Stankiewicz Paweł , Kuechler Alma , Eller C. Daniel , Sahoo Trilochan , Baldermann Christiane , Lieser Ulla , Hesse Martin , Gläser Christiane , Hagemann Monika , Yatsenko Svetlana A. , Liehr Thomas , Horsthemke Bernhard , Claussen Uwe , Marahrens York , Lupski James R. , Hansmann Ingo
Published: February 2006

Few cases of de novo unbalanced X;autosome translocations associated with a normal or mild dysmorphic phenotype have been described. We report a 3‐year‐old dizygotic female twin with prenatally ascertained increased nuchal translucency. Prenatal chromosome studies revealed nearly complete trisomy 15 due to a de novo unbalanced translocation t(X;15)(q22;q11.2) confirmed postnatally. A mild phenotype was observed with normal birth measurements, minor facial dysmorphic features (hypertelorism, short broad nose, and a relatively long philtrum), and moderate developmental delay at the age of 3 years in comparison to her male fraternal twin. Replication timing utilizing BrdU and acridine‐orange staining showed that the der(X) chromosome was late‐replicating with variable spreading of inactivation into the translocated 15q segment. The der(X) was determined to be of paternal origin by analyses of polymorphic markers and CGG‐repeat at FMR1. Methylation analysis at the SNRPN locus and analysis of microsatellites on 15q revealed paternal isodisomy with double dosage for all markers and the unmethylated SNRPN gene. The Xq breakpoint was mapped within two overlapping BAC clones RP11‐575K24 and RP13‐483F6 at Xq22.3 and the 15q breakpoint to 15q11.2, within overlapping clones RP11‐509A17 and RP11‐382A4 that are all significantly enriched for LINE‐1 elements (36.6%, 43.0%, 26.6%, 22.0%, respectively). We speculate that the attenuated phenotype may be due to inactivation spreading into 15q, potentially facilitated by the enrichment of LINE‐1 elements at the breakpoints. In silico analysis of breakpoint regions revealed the presence of highly identical low‐copy repeats (LCRs) at both breakpoints, potentially involved in generating the translocation. © 2006 Wiley‐Liss, Inc.
Inverse association between severe nausea and vomiting in pregnancy and some congenital abnormalities
Authors: Czeizel Andrew E. , Puhó Erzsébet , Ács Nándor , Bánhidy Ferenc
Published: February 2006

The objective of the study was to investigate the possible association between nausea and vomiting in early pregnancy and congenital abnormalities. The prevalence of medically‐recorded severe nausea and vomiting in early pregnancy in cases with congenital abnormalities and their available matched population controls without any defect was compared in the population‐based large data set of the Hungarian Case‐Control Surveillance System of congenital abnormalities, 1980–1996. Of 22,843 cases with as 25 different congenital abnormality groups, 1,713 (7.5%) cases had mothers with medically recorded and treated severe nausea and vomiting during pregnancy. Of 38,151 matched population controls, 3,777 (9.9%) had mothers with severe nausea and vomiting (adjusted prevalence odds ratio (POR) with 95% CI: 0.74, 0.68–0.79). Five congenital abnormality groups: cleft lip with or without cleft palate (0.50, 0.37–0.70), posterior cleft palate (0.53, 0.32–0.89), renal a/dysgenesis (0.23, 0.06–0.96), obstructive defects of urinary tract (0.32, 0.18–0.58), and cardiovascular malformations (0.68, 0.57–0.81) had mothers with a lower prevalence of severe nausea and vomiting in pregnancy (adjusted PORs with 95% CI included in parentheses). Of 25 congenital abnormality groups, 22 had POR lower than 1. Thus in this study the mothers of cases with congenital abnormalities were 26% less likely to have had severe nausea and vomiting in early pregnancy than the mothers of population controls without congenital abnormalities. © 2006 Wiley‐Liss, Inc.
Genotype–phenotype correlation in hereditary hemorrhagic telangiectasia: Mutations and manifestations*
Authors: Bayrak‐Toydemir Pınar , McDonald Jamie , Markewitz Boaz , Lewin Susan , Miller Franklin , Chou Lan‐Szu , Gedge Friederike , Tang Wei , Coon Hillary , Mao Rong
Published: February 2006

Hereditary hemorrhagic telangiectasia (HHT) is a genetically heterogeneous vascular dysplasia with multiple telangiectases and arteriovenous malformations and it is caused by mutations in endoglin gene (ENG) (HHT1) and activin A receptor type II‐like 1 gene (ACVRL1) (HHT2). We evaluated 111 patients with HHT from 34 families by history, examination, screening for vascular malformations, and sequencing of both genes. We found mutations in 26 of the 34 kindreds (76%) analyzed—54% were in ENG and 46% were in ACVRL1. Mutations in ACVRL1 cluster largely in exons 7 and 8, but ENG mutations were widely distributed within that gene. We found that epistaxis had an earlier onset in patients with HHT1 than those with HHT2, but the severity by middle ages was similar. Pulmonary arteriovenous malformations were more frequent and on the average of larger size in HHT1. Hepatic vascular malformations were more common in patients with HHT2. Cerebral arteriovenous malformations were more common in patients with HHT1, but spinal arteriovenous malformations were seen only in patients with HHT2. Truncating mutations in ENG were associated with more affected organs and more severe hemorrhaging than were missense mutations. We conclude that HHT2 has a later onset than HHT1 and the former may disproportionately involve smaller vessels in tissues with more significant vascular remodeling. © 2006 Wiley‐Liss, Inc.
Klinefelter syndrome and mediastinal germ cell tumors
Authors: Völkl Thomas M.K. , Langer Thorsten , Aigner Thomas , Greess Holger , Beck Jörn D. , Rauch Anita M. , Dörr Helmuth G.
Published: February 2006

Precocious puberty is not a typical manifestation of patients with Klinefelter syndrome (KS). However, there is an increased incidence of mediastinal germ cell tumors (M‐GCT) in KS, whereas the discussion of a generally higher tumor risk in this condition is still controversial. A rare subgroup of KS patients consists of prepubertal children with precocious puberty due to human chorionic gonadotropin (hCG)‐producing M‐GCTs. We present clinical data on a boy with KS and sexual precocity, and summarize the published data on 12 boys with KS out of 54 cases of KS and M‐GCT. Clinical report: an 8.5‐year‐old boy presented with signs of precocious puberty. Laboratory analyses (suppressed gonadotropins, elevated testosterone) and thoracic CT demonstrated a β‐human chorionic gonadotropin (β‐hCG) and α1‐feto protein (α‐FP) secreting mediastinal tumor. Histological analysis showed a mixed germ cell tumor comprising choriocarcinoma (CH), embryonal carcinoma (EC), mature teratoma (MT), and yolk sac tumor (YS). He was successfully treated by surgery and adjuvant chemotherapy. Epianalysis of published cases: all KS patients (n = 12), age 4–9 years, presented with precocious sexual development (PP), whereas the older ones showed thorax‐associated symptoms, mainly chest pain, dyspnea, and cough. The histological distribution was also age‐dependent with mixed germ cell tumors predominantly in younger patients. Thus, M‐GCTs are strongly associated with precocious puberty in young boys with KS. Therefore, a karyotype analysis should be included in the clinical work‐up of boys with precocious puberty and M‐GCT. There is still no convincing explanation for the association of M‐GCTs and KS. © 2006 Wiley‐Liss, Inc.
Characterization of two supernumerary marker chromosomes in a patient with signs of Klinefelter syndrome, mild facial anomalies, and severe speech delay*
Authors: Weimer Jörg , Metzke‐Heidemann Simone , Plendl Hansjörg , Caliebe Almuth , Grunewald Regina , Õunap Katrin , Tammur Pille , Jonat Walter , Bartsch Oliver , Siebert Reiner , Arnold Norbert
Published: February 2006

A boy with signs of Klinefelter syndrome, mild facial dysmorphic features, and severely retarded speech development displayed a female karyotype with mosaicism for two marker chromosomes 48,XX,+mar1,+mar2[68]/47,XX,+mar1[19]/47,XX,+mar2[6]/46,XX[8]. Using chromosomal microdissection, locus‐specific fluorescence in situ hybridization (FISH), and PCR with several Y‐chromosome markers, the larger supernumerary marker chromosome (SMC) was characterized as a ring Y‐chromosome. Detection of the SRY‐region explained the male phenotype. The smaller second marker chromosome contained the pericentromeric region of chromosome 8. We suggest that the co‐occurrence of a partial Y‐chromosome and partial trisomy 8 explain the severe speech delay and the facial dysmorphic features. © 2006 Wiley‐Liss, Inc.
A truncating mutation in the IL1RAPL1 gene is responsible for X‐linked mental retardation in the MRX21 family
Authors: Tabolacci Elisabetta , Pomponi M. Grazia , Pietrobono Roberta , Terracciano Alessandra , Chiurazzi Pietro , Neri Giovanni
Published: February 2006

X‐linked mental retardation (XLMR) is a genetically heterogeneous condition, due to mutations in at least 50 genes, involved in functioning of the central nervous system and located on the X chromosome. Nonspecific XLMR (MRX) is characterized essentially by mental retardation transmitted by X‐linked inheritance. More than 80 extended MRX pedigrees have been reported to date, which have been distinguished exclusively by physical position of the corresponding gene on the X chromosome, established by linkage analysis. One such family, MRX21, which was described by us in 1993 and localized to Xp11.4‐pter, has now been reanalyzed with additional markers and after one more affected individual had became available. This extra information allowed a significant reduction of the linkage interval and, eventually, identification of the mutant gene. A stop mutation in exon 10 of the IL1RAPL1 gene (in Xp21) was found in the four affected males and in obligate carriers, allowing conclusive counseling of other family members of uncertain carrier status. The W487X mutation results in the production of a truncated IL1RAPL protein, comprised of the extracellular Ig‐like domain and transmembrane tract, but lacking the last 210 aminoacids of the cytoplasmic domain. MRX21 is the first extended MRX family with a point mutation in IL1RAPL1 and the second with a stop mutation, which had been previously found only in a small family. Our report confirms the role of the IL1RAPL1 gene in causing nonspecific mental retardation in males and underlines the importance of detailed linkage analysis before candidate gene mutational screening. © 2006 Wiley‐Liss, Inc.
Speech and language impairment and oromotor dyspraxia due to deletion of 7q31 that involves FOXP2
Authors: Zeesman Susan , Nowaczyk Małgorzata J.M. , Teshima Ikuko , Roberts Wendy , Cardy Janis Oram , Brian Jessica , Senman Lili , Feuk Lars , Osborne Lucy R. , Scherer Stephen W.
Published: February 2006

We report detailed clinical, cytogenetic, and molecular findings in a girl with a deletion of chromosome 7q31‐q32. This child has a severe communication disorder with evidence of oromotor dyspraxia, dysmorphic features, and mild developmental delay. She is unable to cough, sneeze, or laugh spontaneously. Her deletion is on the paternally inherited chromosome and includes the FOXP2 gene, which has recently been associated with speech and language impairment and a similar form of oromotor dyspraxia in at least three other published cases. We hypothesize that our patient's communication disorder and oromotor deficiency are due to haploinsufficiency for FOXP2 and that her dysmorphism and developmental delay are a consequence of the absence of the other genes involved in the microdeletion. We propose that this patient, together with others reported in the literature, may define a new contiguous gene deletion syndrome encompassing the 7q31‐FOXP2 region. Cytogenetic and molecular analysis of this region should be considered for other individuals displaying similar characteristics. © 2006 Wiley‐Liss, Inc.
Variable contribution of the MTHFR C677T polymorphism to non‐syndromic cleft lip and palate risk in China
Authors: Zhu JiangHui , Ren AiGuo , Hao Ling , Pei LiJun , Liu JianMeng , Zhu HuiPing , Li Song , Finnell Richard H. , Li Zhu
Published: February 2006

Non‐syndromic cleft lip with or without cleft palate (nsCL/P) is one of the most common craniofacial malformations among newborn infants. It has been demonstrated that periconceptional folic acid supplementation may reduce the occurrence of offspring with clefts, particularly in the North China; however, the mechanism remains unknown. Our study of a thermolabile polymorphism (C677T) of methylenetetrahydrofolate reductase (MTHFR) gene in 170 Chinese case‐parent triads revealed a moderate association between this MTHFR polymorphism and nsCL/P in a population from North China, but not in a population from South China. Moreover, the study revealed that the heterozygous parents in the North were about twice as likely to transmit the high‐risk T allele to affected cases, as that observed in the South (OR = 2.24, 95% CI: 1.08–4.65). Thus, the MTHFR polymorphism is a significant risk factor for nsCL/P in this Northern Chinese population. Our study suggested possible genetic heterogeneity in the development of nsCL/P among Northern and Southern populations in China. © 2006 Wiley‐Liss, Inc.
Mitochondrial dysfunction in Brooks–Wisniewski–Brown syndrome
Authors: Morava Eva , Rodenburg Richard , Hol Frans , De Meirleir Linda , Seneca Sara , Busch Rebekka , van den Heuvel Lambert , Smeitink Jan
Published: February 2006

Brooks, Wisniewski, and Brown described a familial presentation of severe developmental retardation, speech delay, static encephalopathy with atrophic hydrocephalus, microcephaly, progressive spastic diplegia, a characteristic facial appearance, optic atrophy, and growth retardation associated with hypoplastic corpus callosum in one of the patients. The authors postulated a distinct X‐linked mental retardation syndrome. Later on a similar phenotype was observed in three male siblings with an early lethal outcome. Here we describe three patients with several overlapping features and a progressive neurological picture presenting with a significantly compromised mitochondrial oxidative phosphorylation measured in a fresh muscle biopsy. Neurological deterioration is a commonly observed feature in mitochondrial disorders. Based on the unique combination of the clinical symptoms, we suggest that our patients have the Brooks–Wisniewski–Brown syndrome. © 2006 Wiley‐Liss, Inc.
Interstitial 2.2 Mb deletion at 9q34 in a patient with mental retardation but without classical features of the 9q subtelomeric deletion syndrome
Authors: Kleefstra Tjitske , Koolen David A. , Nillesen Willy M. , de Leeuw Nicole , Hamel Ben C.J. , Veltman Joris A. , Sistermans Erik A. , van Bokhoven Hans , van Ravenswaay Conny , de Vries Bert B.A.
Published: February 2006

In a female patient with mild mental retardation an interstitial subtelomeric 9q34.3 deletion was identified by a multiplex ligation‐dependent probe amplification (MLPA) based screen for subtelomeric abnormalities. Further characterization of the deletion by high‐resolution tiling path array‐based comparative genomic hybridization (array CGH) revealed a size of 2.2 Mb. The woman lacked the typical 9qter deletion phenotype characteristics, which is inline with the finding that both Eu‐HMTase1 (EHMT) genes were present. However, she presented with mild mental retardation, some mild facial dysmorphisms and aplasia cutis. This is another example of an interstitial subtelomeric deletion, which underscores that further characterizing the precise nature of the deletion is of clinical importance. Moreover, it confirms the importance of the Eu‐HMTase1 gene as the major causative factor of the classical 9qter syndrome phenotype. © 2006 Wiley‐Liss, Inc.
Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): Association between a promoter polymorphism and type 1 diabetes in Asian populations
Authors: Kawasaki Eiji , Awata Takuya , Ikegami Hiroshi , Kobayashi Tetsuro , Maruyama Taro , Nakanishi Koji , Shimada Akira , Uga Mho , Kurihara Susumu , Kawabata Yumiko , Tanaka Shoichiro , Kanazawa Yasuhiko , Lee Inkyu , Eguchi Katsumi ,   Japanese Study Group on Type 1 Diabetes Genetics
Published: February 2006

The protein tyrosine phosphatase, nonreceptor 22 gene (PTPN22) maps to human chromosome 1p13.3‐p13.1 and encodes an important negative regulator of T‐cell activation, lymphoid‐specific phosphatase (Lyp). Recently, the minor allele of a single‐nucleotide polymorphism (SNP) at nucleotide position 1858 (rs2476601, +1858C > T) was found to be associated with type 1 diabetes. However, the degree of the association is variable among ethnic populations, suggesting the presence of other disease‐associated variants in PTPN22. To examine this possibility, we carried out a systemic search for PTPN22 using direct sequencing of PCR‐amplified products in the Japanese population. Association and linkage studies were also conducted in 1,690 Japanese samples, 180 Korean samples, and 472 Caucasian samples from 95 nuclear families. We identified five novel SNPs, but not the +1858C > T SNP. Of these two frequent SNPs, −1123G > C, and +2740C > T were in strong linkage disequilibrium (LD), and the −1123G > C promoter SNP was associated with acute‐onset but not slow‐onset type 1 diabetes in the Japanese population (odds ratio [OR] = 1.42, 95% CI = 1.07–1.89, P = 0.015). This association was observed also in Korean patients with type 1 diabetes (Mantel–Haenszel χ2 = 6.543, P = 0.0105, combined OR = 1.41 95% CI = 1.09–1.82). Furthermore, the affected family‐based control (AFBAC) association test and the transmission disequilibrium analysis of multiplex families of European descent from the British Diabetes Association (BDA) Warren Repository indicated that the association was stronger in −1123G > C compared to +1858C > T. In conclusion, the type 1 diabetes association with PTPN22 is confirmed, but it cannot be attributed solely to the +1858C > T variant. The promoter −1123G > C SNP is a more likely causative variant in PTPN22. © 2006 Wiley‐Liss, Inc.
A novel mutation in the DNA‐binding domain of MAF at 16q23.1 associated with autosomal dominant “cerulean cataract” in an Indian family
Authors: Vanita Vanita , Singh Daljit , Robinson Peter N. , Sperling Karl , Singh Jai Rup
Published: February 2006

Congenital cataract, a clinically and genetically highly heterogeneous eye disorder, is one of the significant causes of visual impairment or blindness in children. It is frequently inherited as an autosomal dominant trait. We investigated a three‐generation family of Indian origin with 12 members affected with cerulean cataract. Linkage analysis was carried out in this family using more than 100 microsatellite markers for the known cataract candidate gene loci. A positive two‐point lod score of 3.9 at θ = 0.000, indicative of linkage, was obtained with three microsatellite markers for chromosome 16. Multipoint and haplotype analysis narrowed the cataract locus to a 15.3 cM region between markers D16S518 and D16S511 that corresponds to the region 16q23.1. Direct sequencing of the candidate gene MAF, which lies in the critical linked region, revealed a novel heterozygous missense mutation in the basic region (BR) of the DNA‐binding domain. This sequence change was considered pathogenic as it segregated in all affected family members, neither seen in unaffected family members nor in 106 unrelated controls. The mutation also results in substitution of highly conserved lysine 297 by arginine (K297R) that affects a residue that forms a part of a predicted DNA‐interaction region of the protein. The association of microcornea with congenital cataract in some affected individuals further underlines the role of the MAF transcription factor in lens and anterior ocular development. Our findings expand the mutation spectrum of MAF in association with congenital cataract and highlight the genetic and phenotypic heterogeneity of congenital cataract. © 2006 Wiley‐Liss, Inc.
Mosaic trisomy 6 and maternal uniparental disomy 6 in a 23‐week gestation fetus with atrioventricular septal defect
Authors: Cockwell Annette E. , Baker Samantha J. , Connarty Margaret , Moore Isabella E. , Crolla John A.
Published: February 2006

Trisomy 6 is seen in early miscarriages in association with an intact, empty amniotic sac or as a pseudomosaic in amniotic fluid cultures. We report the finding of mosaic trisomy 6 in a 23‐week‐gestation pregnancy terminated because of intrauterine death. The post‐mortem showed a well formed macerated male fetus with an atrioventricular septal defect and an exomphalos. By conventional cytogenetics, trisomy 6 was found in 12 out of 25 (48%) fibroblast colonies from fetal skin and 21 out of 32 (66%) colonies derived from amnion, while the remaining metaphases showed an apparently normal male karyotype. Molecular genetic studies on DNA from uncultured fetal skin and cord samples using polymorphic microsatellite repeat sequences showed no evidence of trisomy 6, but demonstrated that both chromosome 6 homologs were of maternal origin consistent with maternal uniparental disomy (UPD). © 2006 Wiley‐Liss, Inc.
Ring chromosome 4 and Wolf–Hirschhorn syndrome (WHS) in a child with multiple anomalies
Authors: Balcı Sevim , Engiz Özlem , Aktaş Dilek , Vargel Ibrahim , Beksaç M.S. , Mrasek Kristin , Vermeesch Joris , Liehr Thomas
Published: February 2006

We report on a 16‐month‐old male patient with ring chromosome 4 and deletion of Wolf–Hirschhorn syndrome (WHS) region with multiple congenital anomalies including unilateral cleft lip and palate, iris coloboma, microcephaly, midgut malrotation, hypospadias, and double urethral orifices. Peripheral chromosome analysis of the patient showed 46,XY,r(4)(p16.3q35) de novo. Multicolor fluorescence in situ hybridization (FISH) study was also performed and according to multicolor banding (MCB) a r(4)(::p16.3 → q34.3 ∼ 35.1::) was found in all metaphases. Subtelomeric 4p region, subtelomeric 4q region, as well as, Wolf–Hirschhorn critical region were deleted in ring chromosome 4. Genomic microarray analysis was also performed to delineate the size of deletion. Cranial magnetic resonance imaging (MRI) showed hypoplastic corpus callosum, delayed myelinization, and frontal and occipital lobe atrophies. Both maternal and paternal chromosomal analyses were normal. We compare the phenotypic appearance of our patient with the previously reported 16 cases of ring chromosome 4 in the medical literature. © 2006 Wiley‐Liss, Inc.
A 9‐year‐old male with a duplication of chromosome 3p25.3p26.2: Clinical report and gene expression analysis
Authors: Bittel Douglas C. , Kibiryeva Nataliya , Dasouki Majed , Knoll Joan H.M. , Butler Merlin G.
Published: February 2006

We describe a 9‐year‐old male referred for genetic evaluation for Prader‐Willi syndrome (PWS). PWS is the most common genetically defined cause of life‐threatening obesity and results from a functional loss of paternally expressed genes from the chromosome 15q11‐q13 region. The patient presented with pervasive developmental disorder, delayed speech, and rapid onset of obesity at age 4 years, all features similar to PWS. However, chromosome 15q11‐q13 methylation testing and fragile X studies were normal. GTG‐banding and fluorescence in situ hybridization (FISH) with whole chromosome 3 paint probe (WCP3) and a chromosome 3p subtelomeric probe suggested a duplication of 3p25.3p26.2, a finding supported by comparative genomic hybridization (CGH). This region of chromosome 3p contains genes which contribute to obesity and behavioral problems, most notably, ghrelin (GHRL), an oxytocin receptor (OXTR), solute carrier family six members (gamma‐aminobutyric acid (GABA) neurotransmitter transporters, SLC6A1 and SLC6A11), and peroxisome proliferator‐activated receptor gamma (PPARG). To characterize these obesity and behavior related genes in our subject, we performed quantitative RT‐PCR and compared expression levels with similarly aged male subjects (four non‐obese males, four obese males, and four PWS males—two with 15q11‐q13 deletions and two with maternal disomy 15). Our studies suggest increased expression of several genes in the 3p duplication region, including GHRL and PPARG, which may contribute to the phenotypic features in our 3p duplication subject. © 2006 Wiley‐Liss, Inc.
A nonsense mutation of PEPD in four Amish children with prolidase deficiency
Authors: Wang Heng , Kurien Biji T. , Lundgren David , Patel Nisha C. , Kaufman K. M. , Miller David L. , Porter Andrew C. , D'Souza Anil , Nye Leah , Tumbush John , Hupertz Vera , Kerr Douglas S. , Kurono S. , Matsumoto H. , Scofield R. Hal
Published: February 2006

Encoded by the peptidase D (PEPD) gene located at 19q12‐q13.11, prolidase is a ubiquitous cytosolic enzyme that catalyzes hydrolysis of oligopeptides with a C‐terminal proline or hydroxyproline. We describe here four Amish children with a severe phenotype of prolidase deficiency in the Geauga settlements of Ohio as the first report of prolidase deficiency in the Amish population as well as in the United States. The patients presented with infection, hepatosplenomegaly, or thrombocytopenia, in contrast to most cases previously reported in the literature, presenting with skin ulcers. All four patients had typical facial features, classic skin ulcers, and multisystem involvement. Recurrent infections, asthma‐like chronic reactive airway disease, hyperimmunoglobulins, hepatosplenomegaly with mildly elevated aspartate transaminase (AST), anemia, and thrombocytopenia were common and massive imidodipeptiduria was universal. Prolidase activity in our patients is nearly undetectable. Direct sequencing of PCR‐amplified genomic DNA for all of the exons from the four patients revealed the same homozygous single nucleotide mutation c.793 T > C in exon 11, resulting in a premature stop‐codon at amino acid residue 265 (p.R265X). It is speculated that the severe phenotype in these patients might be associated with the type of the PEPD gene mutation. © 2006 Wiley‐Liss, Inc.
Molecular cytogenetic analysis of a familial interstitial deletion Xp22.2‐22.3 with a highly variable phenotype in female carriers
Authors: Chocholska Sylwia , Rossier Eva , Barbi Gotthold , Kehrer‐Sawatzki Hildegard
Published: February 2006

We describe a familial interstitial deletion of 7.7‐Mb involving Xp22.2‐22.3. The deletion was transmitted from an asymptomatic mother to her two children with severe developmental delay, no speech development and autistic behavior. Assessment of the deletion boundaries by FISH and PCR analyses indicated that the deletions encompasses 27 genes. Several of these genes are associated with known disorders, like KAL1 (Kallmann syndrome), steroid sulfatase (STS) (X‐linked ichtyosis), and arylsulfatase E (ARSE) (chondrodysplasia punctata). The deletion also includes all four VCX genes (VCX‐A, VCX‐B1, VCX‐B, and VCX‐C) and the neuroligin 4 (NLGN4) gene. VCX‐A deficiency has been shown previously to be associated with mental retardation and NLGN4 mutations lead to mental retardation in conjunction with autism. Functional deficiency of both MRX genes, VCX‐A and NLGN4, are most likely associated with the impaired cognitive development of the patients described here. The phenotype associated with the Xp deletion was highly variable in female carriers and might be attributed to unfavorable X inactivation. However, all the 27 genes included in the deleted interval escape X inactivation and are expressed at variable levels from the normal X chromosome. Thus, the overall X inactivation pattern and inter‐individual expression variability of the genes in distal Xp might be determinants of the phenotype associated with the deletion. © 2006 Wiley‐Liss, Inc.
Eliminating unconscionability in assessing mandatory clauses by deploying the ‘vantage point of public policy’
Authors: Marrow Paul Bennett
Published: February 2006

Paul Bennett Marrow, of Chappaqua, N.Y., describes why analyzing arbitration clauses with an unconscionability standard doesn't provide useful precedent, and why courts should look to public policy in reviewing contract terms.
Brain imaging evidence of preclinical Alzheimer's disease in normal aging
Authors: Jagust William , Gitcho Amy , Sun Felice , Kuczynski Beth , Mungas Dan , Haan Mary
Published: February 2006

Objective

This study was designed to test the hypothesis that baseline glucose metabolism and medial temporal lobe brain volumes are predictive of cognitive decline in normal older people.

Methods

We performed positron emission tomography using [18F]fluorodeoxyglucose and structural magnetic resonance imaging at baseline in 60 cognitively normal community‐dwelling older subjects who were part of a longitudinal cohort study. Subjects were followed for a mean of 3.8 years, with approximately annual evaluation of global cognition (the Modified Mini‐Mental State Examination) and episodic memory (delayed recall). Baseline brain volumes and glucose metabolism were evaluated in relation to the rate of change in cognitive test scores.

Results

Six subjects developed incident dementia or cognitive impairment (converters). Baseline positron emission tomography scans showed regions in left and right angular gyrus, left mid‐temporal gyrus, and left middle frontal gyrus that predicted the rate of change on the Modified Mini‐Mental State Examination (p < 0.001). The left hemisphere temporal and parietal regions remained significant when converters were excluded. Both hippocampal (p = 0.03) and entorhinal cortical volumes (p = 0.01) predicted decline on delayed recall over time, and entorhinal cortical volumes remained significant when converters were excluded (p = 0.02). These brain volumes did not predict Modified Mini‐Mental State Examination decline.

Interpretation

These results indicate that temporal and parietal glucose metabolism predict decline in global cognitive function, and medial temporal brain volumes predict memory decline in normal older people. The anatomical location of these findings suggests detection of preclinical Alzheimer's disease pathology. Ann Neurol 2006
Das Reaktivitäts‐Selektivitäts‐Prinzip: ein unzerstörbarer Mythos der organischen Chemie
Authors: Mayr Herbert , Ofial Armin R.
Published: February 2006

Das Reaktivitäts‐Selektivitäts‐Prinzip (RSP), früher ein unumstrittener Lehrsatz der organischen Chemie, wurde in den 1970er Jahren ausgehöhlt und um 1980 mehr oder weniger aufgegeben. Obwohl nun seit mehr als 25 Jahren klar ist, dass abnehmende Selektivität als Folge zunehmender Reaktivität nur dann erwartet werden kann, wenn man sich auf die Diffusionsgrenze zu bewegt, lebt das RSP als intuitiv eingängige Regel weiter. Dieser Kurzaufsatz zeigt, warum es überhaupt nicht möglich sein kann, dass die Selektivität mit zunehmender Reaktivität generell abnimmt, und beleuchtet die Schwachstellen der theoretischen Grundlagen des RSP.
The Reactivity–Selectivity Principle: An Imperishable Myth in Organic Chemistry
Authors: Mayr Herbert , Ofial Armin R.
Published: February 2006

The reactivity–selectivity principle (RSP), once a tenet of organic chemistry, eroded during the 1970s and was more or less abandoned by 1980. Although it has been clear for more than 25 years that a decrease in selectivity with increasing reactivity can only be expected with certainty if diffusion control is approached, the RSP has survived as an intuitively appealing rule. This Minireview shows why selectivity cannot generally decrease with increasing reactivity and highlights the weaknesses of the theoretical foundations of the RSP.
Palladium‐catalyzed selective alkoxycarbonylation of N‐vinylphthalimide
Authors: Zhu Bing Chun , Jiang Xuan Zhen
Published: February 2006

The palladium‐catalyzed selective alkoxycarbonylation of enamide was studied using N‐vinylphthalimide as the model substrate. Both palladium (0) and palladium (II) compounds can be used as the catalyst precursors. It was found that the efficiency and the regioselectivity of the reaction depended remarkably on phosphine ligands and other reaction parameters such as solvent, substrate concentration, temperature and promoters. Good yields and high regioselectivities of either the branched or linear products were obtained under optimum reaction conditions. The primary optical yield (12.3%) of N‐Phthaloyl‐L‐alanine methyl ester (2) was obtained using (S)‐(+)‐BNPPA as the chiral ligand. A possible reaction mechanism for the alkoxycarbonylation of N‐vinylphthalimide was also proposed. Copyright © 2006 John Wiley & Sons, Ltd.
Identification of nucleation loci in emulsion polymerization processes. I. New information from spectroscopy studies
Authors: Shastry Vineet , Garcia‐Rubio L. H.
Published: February 2006

Particle nucleation is the forcing function in emulsion polymerization reactions and as such it plays a significant role in the development of most of the properties of the final latex. The locus of nucleation in emulsion polymerization remains a contentious issue. Recent developments in the spectroscopy of emulsions strongly suggest that the locus of particle nucleation is a population of small nano‐droplets of size range between 30–100 nanometers in diameter. These nano‐droplets are generated independently of the rate of initiator decomposition and appear to be functions only of the emulsification conditions. In this paper the simulation studies leading to the identification of the nano‐droplet population are described. The theoretical evidence suggesting that the nano‐droplets are the main loci of particle nucleation is presented and along with the recommendations for the experimental work. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2847–2857, 2006
Effect of structural relaxation at physiological temperature on the mechanical property of poly(L‐lactic acid) studied by microhardness measurements
Authors: Wang Yaming , Mano João F.
Published: February 2006

Besides hydrolysis, the physical properties of poly(L‐lactic acid), PLLA, may change, at a shorter time‐scale, at physiological temperature, because of structural relaxation. This process may be relevant as it may contribute for the time‐dependent modifications of the mechanical performance of PLLA‐based implants, or in other properties such as specific volume or permeability. In this work, microhardness was measured at room temperature after ageing poly(L‐lactic acid) samples at 37°C during different periods, ranging from 15 min to 15 days. For the PLLA analyzed, the initial Vickers microhardness was around 140 MPa and an increase higher than 55% was observed in a time span of 15 days. The relaxation of enthalpy at 37°C was also monitored by differential scanning calorimetry, and both results were successfully described by a simple model that considers a nonexponential evolution of the quantities sensitive to physical ageing. The time‐scales of the structural relaxation probed by microhardness or by enthalpy were different, and the results suggested that the evolution of the mechanical property was slower than the later. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2628–2633, 2006
Role of mixing parameters in the preparation of poly(ethylene vinyl acetate) nanocomposites by melt blending
Authors: Tillekeratne Mangala , Jollands Margaret , Cser Ferenc , Bhattacharya Sati N.
Published: February 2006

Polymer/layered‐silicate nanocomposites have gathered momentum as cost‐effective and versatile materials since the middle of the 20th century. Many publications discuss the chemistry of organomodification and properties of nanocomposites, but relatively few deal with the significance of processing conditions. This article takes into account three mixing parameters and discusses the contribution of each toward nanocomposite formation. Organomodified natural sodium‐type bentonite clay was used in this study. The nanocomposites formed were characterized by X‐ray diffraction and mechanical property tests. Response surface regression was used to optimize the tensile modulus. The analysis shows that nanocomposite formation is promoted by a diffusion mechanism and that the interactions of parameters are as important as individual parameters. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2652–2658, 2006
Evaluation of fiber wettability based on an immerging force measurement
Authors: Xiao Hong , Yu Weidong , Shi Meiwu
Published: February 2006

This article provides a new approach to estimate the wettability of fibers based on the force analysis in immerging procedure. A fiber in horizontal is forced into and withdrawn from the liquid at a certain speed, and the force changes are detected simultaneously. The experimental results show that the force impulse can be found at fiber contacting with liquid and immersed into liquid, and its value depends on the wettability of the fiber. According to the force impulses of different fibers, the immerging behavior of the fibers can be obtained and categorized into four characteristics. Meanwhile, the wettability of the fibers can be evaluated with the wettability factor, w, derived from the fiber immerging curve, where w is the ratio of the force increment on fiber initially contacting with the liquid to the force increment on liquid surface closing with fiber immerging into the liquid, and with the contact angle, θ, calculated from the wettability factor (θ = π/(w+1)) supposed that the fiber is a circular cross section. The pulling‐out test for a fiber has also been conducted and the results are discussed briefly in this article. The force measurement indicates that the method can be used for various fibers with short length, or lower density than that of the liquid, or poor wettability. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2659–2666, 2006
Preparation by melt mixing and characterization of isotactic polypropylene/SiO2 nanocomposites containing untreated and surface‐treated nanoparticles
Authors: Bikiaris Dimitris N. , Papageorgiou George Z. , Pavlidou Eleni , Vouroutzis Nikolaos , Palatzoglou Paraskevas , Karayannidis George P.
Published: February 2006

In the present study two series of isotactic polypropylene (iPP)/SiO2 nanocomposites containing 1, 2.5, 5, 7.5, and 10 wt % SiO2 nanoparticles were prepared by melt‐mixing on a twin‐screw corotating extruder. In the first series untreated fumed silica nanoparticles were used, whereas in the second nanoparticles were surface‐treated with dimethyldichlorosilane. In both cases, the average size of the primary nanoparticles was 12 nm. Tensile and impact strength were found to increase and to be affected mainly by the type and content of silica nanoparticles. A maximum was observed, corresponding to samples containing 2.5 wt % SiO2. These findings are discussed in light of the SEM and TEM observations. By increasing the amount of nanoparticles, large aggregates of fumed silica could be formed, which may explain the reduction of mechanical properties with higher concentrations of SiO2. However, it was found that surface‐treated nanoparticles produced larger aggregates than did those derived from untreated nanoparticles, despite the increased adhesion of the iPP matrix, as was postulated from yield strength. This behavior negatively affected mechanical properties. In addition, an effort was made to determine if toughening theories, mainly the critical interparticle distance for rubber toughening or composites, also might be applicable in nanocomposites. From DSC measurements it was demonstrated that silica nanoparticles acted as effective nucleating agents, increasing the crystallization rate and the degree of crystallinity of iPP. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2684–2696, 2006
Improving easy care nonformaldehyde finishing performance using polycarboxylic acids via precationization of cotton fabric
Authors: Hebeish A. , Hashem M. , Abdel‐Rahman A. , El‐Hilw Z. H.
Published: February 2006

Cotton fabric were first subjected to quaternization (cationization) reaction using 3‐chloro‐2‐hydroxypropyl trimethyl ammonium chloride commercially known as Quat®‐188. Cationization was carried out under different conditions for optimization of the preparation of cationized cotton with different degrees of cationization, using the pad‐batch method. Also, established was the optimal condition for cationization that involves Quat‐188/NaOH molar ratio 1/2 at 70°C for 4 h. Besides, a thorough investigation of factors affecting reaction of these cationized cotton with citric acid (CA) or 1,2,3,4‐butanetetracarboxylic acid (BTCA) was carried out with a view of improving the ease of care characteristics of nonformaldehyde finishing. The dependence of fabric performance as measured by strength properties, dry wrinkle recovery angles, whiteness index, and dyeability with reactive dyes was also evaluated. It was postulated that reaction of cationized cotton with either CA or BTCA involves estercrosslinking as well as ionic crosslinking. This, indeed, was largely positively reflected on the fabric performance especially when the properties of both uncationized cotton were compared with those of the cationized cotton. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2697–2704, 2006
Synthesis and adsorption properties of metal ions of novel azacrown ether crosslinked chitosan
Authors: Zhang Xueyong , Ding Shimin , Wang Yuting , Feng Xianghua , Peng Qi , Ma Shulan
Published: February 2006

Azacrown ether chitosan (CTSC) was synthesized by the reaction of chitosan with N‐allyl benzo 15‐crown‐5 crown ether. Azacrown ether crosslinked chitosan (CCTSC) was prepared by the crosslinked reaction of CTSC and epichlorodydrin. Their structures were confirmed by infrared spectral analysis and X‐ray diffraction analysis. The adsorption properties of CTSC and CCTSC for metal ions were also investigated. The experimental results showed that the two chitosan derivatives not only had a good capacity to adsorb Pd2+ and Ag+ but also was highly selective for Pd2+ and Ag+ in the coexistence system containing other metal ions. At 20°C ± 1°C and pH = 4, the adsorption capacity of CTSC and CCTSC for Pd2+ was 186.1 and 173.1 mg/g, respectively; and for Ag+ was 90.2 and 56.5 mg/g, respectively. The selectivity coefficients were K = 6.99, K = ∞, K = 35.38, K = ∞ for CTSC and K = 10.66, K = ∞, K = 85.45, K = ∞ for CCTSC. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2705–2709, 2006
Fabrication of arrays of silver nanoparticle aggregates by microcontact printing and block copolymer nanoreactors
Authors: Cong Yang , Fu Jun , Zhang Zexin , Cheng Ziyong , Xing Rubo , Li Jian , Han Yanchun
Published: February 2006

A combination of microcontact printing and block copolymer nanoreactors succeeded in fabricating arrays of silver nanoparticle aggregates. A complex solution of polystyrene‐block‐poly(4‐vinylpyridine) micelles and silver salt was used as an ink to form thin films or droplets on polydimethylsiloxane stamp protrusions. After these complex aggregates were printed onto silicon substrates under controlled conditions, highly ordered arrays of disklike, dishlike, and dotlike complex aggregates were obtained. A subsequent oxygen reactive ion etching treatment yielded arrays of silver nanoparticle aggregates. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2737–2743, 2006
Factorial experimental design for graft copolymerization of styrene and methyl methacrylate onto styrene–butadiene rubber
Authors: Arayapranee W. , Prasassarakich P. , Rempel G. L.
Published: February 2006

The graft copolymerization of styrene (ST) and methyl methacrylate (MMA) onto styrene–butadiene rubber (SBR) latex prepared by seeded emulsion polymerization has been studied under various reaction conditions using cumene hydroperoxide redox initiator. The mechanism of graft copolymerization has been investigated. The synthesized graft copolymers were purified and then characterized by proton nuclear magnetic resonance (1H NMR) analysis. A 2 2 fractional factorial experimental design was applied to study the effects of the process variables such as the amount of initiator and emulsifier, the presence or absence of chain‐transfer agent, ST to MMA ratio, monomer to rubber ratio, and reaction temperature on the grafting efficiency. The analysis of the results from the design showed the sequence of the main effect on the observed response of the grafting of ST and MMA onto SBR and that the amount of chain‐transfer agent had a significant effect. Transmission electron microscopy was used to study the morphology of the graft copolymers. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 2867–2874, 2006