bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and incidence in women with 47,XXX and variants
Authors: Stochholm Kirstine , Juul Svend , Gravholt Claus Højbjerg 
Published: January 2010

Abstract47,XXX syndrome is among the most common sex chromosomal disorders; however, apart from screening surveys, epidemiological data are limited. We report data on 136 women diagnosed with 47,XXX or a compatible karyotype in Denmark during 1963–2008. We identified an incidence of 10.7 per 100,000 liveborn girls, which was lower than expected and was stable during the study period. Age at diagnosis ranged from 0 to 73 years, with a diagnostic delay of 18.2 years or more in half the 47,XXX persons. We compared persons with 47,XXX with an age‐matched cohort of the female background population (born same year and month), identified in Statistics Denmark (n = 13,400). Mortality was significantly increased in total with a hazard ratio of 2.5 (1.6–3.9), corresponding to a difference in median survival of 7.7 years. When we divided causes of death into 19 chapters according to the International Classification of Diseases, a generally increased mortality was identified in all informative chapters. Furthermore, we identified significantly increased mortality in cardiovascular diseases, in the chapter concerning chromosomal and congenital defects, and in the chapter of unspecified diseases. Better delineation of the clinical phenotype of 47,XXX is needed; available information does not readily explain the increased mortality. © 2010 Wiley‐Liss, Inc.
Terminal 3p deletions in two families—Correlation between molecular karyotype and phenotype
Authors: Pohjola Pia , de Leeuw Nicole , Penttinen Maila , Kääriäinen Helena 
Published: January 2010

AbstractThe 3p deletion syndrome is a rare disorder caused by deletions of different sizes in the 3p25‐pter region. It is characterized by growth retardation, developmental delay, mental retardation, dysmorphism, microcephaly, and ptosis. The phenotype of individuals with deletions varies from normal to severe. Most cases occur de novo, but a few familial cases have been reported. We describe two families with terminal 3p deletions and extremely variable clinical features. In family A, the mother and daughter were extremely mildly affected whereas the son had more severe clinical features. In family B, the mother was normal and her son was affected, having some symptoms that had not been described in the 3p deletion syndrome before. The deletions were characterized by genome‐wide SNP array analysis and were 9 and 1.1 Mb in size. Sequencing analysis of the CHL1, CNTN4, and CRBN genes did not reveal any masked recessive alleles that might explain the more severe phenotypes in the probands. In family A, the 9 Mb deletion can be considered causal for the 3p deletion syndrome in the proband, but the extremely mild phenotype in the other family members remains unexplained. In family B, the 1.1 Mb terminal deletion encompasses only the CHL1 gene, which is insufficient to cause 3p deletion symptoms; thus the clinical features observed in this family may have a different cause. The variable penetrance of 3p deletions creates challenges in genetic counseling, as the phenotype of the offspring cannot be predicted based on chromosomal and/or genome‐wide array analytical findings. © 2010 Wiley‐Liss, Inc.
Identification of a 21q22 duplication in a Silver–Russell syndrome patient further narrows down the Down syndrome critical region
Authors: Eggermann Thomas , Schönherr Nadine , Spengler Sabrina , Jäger Susanne , Denecke Bernd , Binder Gerhard , Baudis Michael 
Published: January 2010

AbstractSeveral duplications of chromosome 21q helped to narrow down the Down syndrome (DS) critical region (DSCR) to chromosomal band 21q22 with an approximate length of 5.4 Mb. Recently, it has been suggested that the facial gestalt of DS has been linked to the distal part of the DSCR whereas the proximal region harboring DSCR1/RCAN and DSCAM should be associated with the cardiac abnormalities. Here, we report on a patient with Silver–Russell syndrome (SRS) and a paternally inherited 0.46 Mb duplication in 21q22 affecting the KCNE1 and DSCR1/RCAN genes. The identification of an involvement of KCNE1 was interesting because it encodes the β‐subunit of the KvLQT1 channel as the slow component of the cardiac delayed rectifier K+ current. Since duplication of the KCNQ1 gene encoding the α‐subunit of the same channel was reported recently in another SRS patient, we screened both genes for mutations in a cohort of SRS patients without detecting pathologic variants. We presume that the duplication of the two functionally linked genes in different patients with the same disorder is a coincidental finding. However, the lack of DS typical clinical features in our case allows us to further narrow down the DSCR in 21q22. We conclude that DSCR1/RCAN is not sufficient for generating phenotypic features associated with DS but our observation does not contradict a possible role for DSCR1/RCAN in mediating DYRK1A‐based effects. © 2010 Wiley‐Liss, Inc.
Deletion of 7q11.21‐q11.23 and infantile spasms without deletion of MAGI2
Authors: Röthlisberger Benno , Hoigné Irène , Huber Andreas R. , Brunschwiler Wolfgang , Capone Mori Andrea 
Published: January 2010

AbstractWe report on the clinical and cytogenetic findings and on the array‐based characterization of an interstitial 7q11.21‐q11.23 deletion initially recognized by standard karyotyping in a 15‐month‐old female patient. Beginning at the age of 3 months and 2 weeks the patient had severe infantile spasms. Recently, it was reported that infantile spasms are associated with deletion of the MAGI2 gene on chromosome 7q11.23. Nevertheless, not all patients reported with deletions of MAGI2 developed infantile spasms and at least one reported patient with a deletion 7q11.23 without missing the MAGI2 gene was diagnosed with infantile spasms. Molecular karyotyping of our patient confirmed a large 13 Mb deletion encompassing the 7q11.21‐q11.23 region without involvement of MAGI2. Critical review of published data and the results of our patient underline the importance to map precisely the deletion boundaries of further patients to reevaluate the significance of MAGI2 hemizygosity in the pathogenesis of infantile spasms. © 2010 Wiley‐Liss, Inc.
Novel frameshifting mutations of the ZMPSTE24 gene in two siblings affected with restrictive dermopathy and review of the mutations described in the literature
Authors: Smigiel Robert , Jakubiak Aleksandra , Esteves‐Vieira Vera , Szela Katarzyna , Halon Agnieszka , Jurek Tomasz , Lévy Nicolas , De Sandre‐Giovannoli Annachiara 
Published: January 2010

AbstractRestrictive dermopathy (RD) is a rare, severe, lethal genodermatosis in which tautness of the skin causes fetal akinesia or hypokinesia deformation sequence. To date, about 60 cases of RD were described. The signs of the disease are very characteristic and include intrauterine growth retardation, thin, tightly adherent translucent skin, superficial vessels, typical facial dysmorphism as well as generalized joint contractures. The syndrome is caused in most cases by ZMPSTE24 autosomal recessive mutations, or, less frequently, by LMNA autosomal dominant mutations. We report on two brothers affected with RD, who died in the neonatal period. Molecular analyses were performed in the second child, for whom biological material was available, and both parents. Compound heterozygous frameshifting mutations were identified in exon 1 (c.50delA) and exon 5 (c.584_585delAT) of the ZMPSTE24 gene. The autosomal recessive inheritance was confirmed by the parents' genomic analysis. Besides, a review of the mutations causing RD is made. © 2010 Wiley‐Liss, Inc.
OEIS complex associated with chromosome 1p36 deletion: A case report and review
Authors: El‐Hattab Ayman W. , Skorupski Josh C. , Hsieh Michael H. , Breman Amy M , Patel Ankita , Cheung Sau Wai , Craigen William J. 
Published: January 2010

AbstractOEIS complex (Omphalocele, Exstrophy of the cloaca, Imperforate anus, and Spine abnormalities) is a rare defect with estimated incidence of 1 in 200,000 live births. Most cases are sporadic, with no obvious cause. However, it has been rarely reported in patients with family members having similar malformations or with chromosomal anomalies. In addition, OEIS complex has been observed in association with environmental exposures, twinning, and in vitro fertilization. Monosomy 1p36 is the most common terminal deletion syndrome, with a prevalence of 1 in 5,000 newborns. It is characterized by specific facial features, developmental delay, and heart, skeletal, genitourinary, and neurological defects. We describe an infant with OEIS complex and 1p36 deletion who had features of both disorders, including omphalocele, cloacal exstrophy, imperforate anus, sacral multiple segmentation, renal malposition and malrotation, genital anomalies, diastasis of the symphysis pubis, microbrachycephaly, large anterior fontanel, cardiac septal defects, rib fusion, a limb deformity, developmental delay, and typical facial features. Chromosomal microarray analysis detected a 2.4 Mb terminal deletion of chromosome 1p. This is the first reported case with OEIS complex in association with a chromosome 1p36 deletion. © 2010 Wiley‐Liss, Inc.
Delineation of a 1.65 Mb critical region for hemihyperplasia and digital anomalies on Xq25
Authors: Ricks Christian B. , Masand Ruchi , Fang Ping , Roney Erin K. , Cheung Sau Wai , Scott Daryl A. 
Published: January 2010

AbstractDuplications involving portions of the long arm of the X‐chromosome can be associated with mental retardation, short stature, microcephaly, panhypopituitarism, and a wide range of physical findings. Less common are duplications in distal Xq associated with hemihyperplasia and digital anomalies. We report on a 4‐year‐old female with hemihyperplasia, syndactyly of fingers and toes, bilateral 5th finger clinodactyly, short stature, developmental delay, and microcephaly associated with an 11.2 Mb duplication of Xq25–Xq27.1. The boundaries of this duplication were mapped using high resolution array comparative genome hybridization and follow‐up studies revealed that the same duplication was carried by the patient's mother who has short stature and cognitive disabilities. Using the duplication boundaries from this case, and data from previously published reports, we have delineated a 1.65 Mb critical region for hemihyperplasia and digital anomalies on chromosome Xq25. Based on these findings physicians should consider obtaining array comparative genome hybridization studies on individuals with hemihyperplasia especially when accompanied by digital findings since identification of an Xq25 duplication can dramatically change recurrence risk estimations and may also provide insight into the possible comorbidities. © 2010 Wiley‐Liss, Inc.
Speech–language characteristics of children with neurofibromatosis type 1
Authors: Thompson Heather L. , Viskochil David H. , Stevenson David A. , Chapman Kathy L. 
Published: January 2010

AbstractDelays in speech and articulation development have been found in school‐aged children and adolescents with neurofibromatosis type 1 (NF1). This report examines speech and language skills of preschool children with NF1. Nineteen 3‐ to 5‐year‐old children diagnosed with NF1 were assessed using measures of articulation (GFTA‐2), and receptive and expressive language (CELF‐P2). Significant differences were observed between mean scores obtained by the group of children with NF1 compared to the validated controls from the speech and language instruments (P ≤ 0.009). Sixty‐eight percent of the children exhibited delays in speech and/or language. Thirty‐two percent demonstrated delays in articulation, 37% percent demonstrated delays in receptive language, and 37% exhibited delays in expressive language. Sixteen percent of the children exhibited a voice disorder and 42% were judged to have a resonance problem. No significant differences were observed on any of the measures of speech and language for children with non‐familial versus familial NF1. Results of this study support the need for early assessment of speech and language problems for children diagnosed with NF1 and implementation of appropriate timely intervention as needed. © 2010 Wiley‐Liss, Inc.
8q23‐q24 duplication—further delineation of a rare chromosomal abnormality
Authors: Wheeler Patricia G. 
Published: January 2010

AbstractPresented here is a young girl with a rare interstitial duplication of 8q23.3‐q24.21. At birth, unusual facial features led to karyotype analysis with a finding of increased material in 8q. Specific determination of where the extra material came from required comparative genomic hybridization (CGH). The affected girl has dysmorphic facial features including hypertelorism, a wide nasal bridge, retrognathia, hyperopic astigmatism, hirsutism, and developmental delay. The area duplicated includes at least 47 genes including TRPS1 and EXT1. Her features will be described and compared to two similar cases. © 2010 Wiley‐Liss, Inc.
Acute lymphoblastic leukemia in Weaver syndrome
Authors: Basel‐Vanagaite Lina 
Published: January 2010

AbstractWeaver syndrome comprises pre‐ and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance and developmental delay; it is a generally sporadic disorder, although autosomal dominant inheritance has been reported. Some of the manifestations characterize both the Weaver and Sotos syndrome, and distinction between the two is mainly by clinical examination and molecular testing. Most of the patients with Sotos syndrome have NSD1 gene deletions or mutations; however, the molecular basis of most of the Weaver syndrome patients is unknown. Patients with overgrowth syndromes have an increased frequency of tumors; the risk in Sotos syndrome patients has been estimated to be about 2–3%, with leukemia and lymphoma accounting for 44% of the malignancies. We report on a $4{\raise0.5ex\hbox{$\scriptstyle 1$}\kern-0.1em/\kern-0.15em\lower0.25ex\hbox{$\scriptstyle 2$}}$‐year‐old girl with typical Weaver syndrome who developed acute lymphoblastic leukemia, an association not previously reported, and review the reported cases of Weaver syndrome patients who developed malignancies. Malignancy in Weaver syndrome has been reported previously in six patients. While searching the literature for all reported cases with Weaver syndrome and counting the cases with malignancy, we found that the frequency of tumors or hematologic malignancy was 10.9%. This is likely to be an overestimate, biased by failure to report cases without tumors and by over‐reporting cases with this rare association. While the presence of acute lymphoblastic leukemia in our patient might be incidental, we cannot exclude a possible causative association between Weaver syndrome and hematologic malignancy. © 2010 Wiley‐Liss, Inc.
Progressive aortic root and pulmonary artery aneurysms in a neonate with Loeys–Dietz syndrome type 1B
Authors: Muramatsu Yukako , Kosho Tomoki , Magota Miyuki , Yokotsuka Taro , Ito Masatoki , Yasuda Ayako , Kito Osamu , Suzuki Chizuko , Nagata Yoshie , Kawai Satoru , Ikoma Masanobu , Hatano Tameo , Nakayama Masato , Kawamura Rie , Wakui Keiko , Morisaki Hiroko , Morisaki Takayuki , Fukushima Yoshimitsu 
Published: January 2010

AbstractLoeys–Dietz Syndrome (LDS) is an autosomal dominant aortic aneurysm syndrome with multisystem involvement, caused by heterozygous mutations of transforming growth factor β receptor type 1 (TGFBR1) or type 2 (TGFBR2) genes. We report on a neonate with the disorder caused by a known TGFBR2 mutation, who developed neonatal‐onset progressive dilation of the aortic valve and aneurysms of the aortic root and main pulmonary artery (PA) associated with a large left‐to‐right shunt via a ventricular septal defect (VSD) and an atrial septal defect. He also had skeletal features (flexion contractures of the fingers, talipes equinovarus, a cleft palate, and joint laxity), mild facial dysmorphisms, and developmental delay. The dilation and aneurysms progressed after PA banding at age 12 days; and the patient received an intracardiac repair of the defects and PA plasty at age 42 days, followed by no further progression of the dilation and the aneurysms. Neonates with generalized hypotonia, a cleft palate, inguinal herniae, musculoskeletal features such as camptodactyly and talipes equinovarus, and a cardiac murmur should be suspected to have LDS, and extensive cardiovascular evaluation and testing of TGFBR1 and TGFBR2 are recommended. LDS patients with cardiac defects that lead to a large left‐to‐right shunt and congestive heart failure such as VSD should be considered for intracardiac repair even in early infancy. © 2010 Wiley‐Liss, Inc.
A review of facial image analysis for delineation of the facial phenotype associated with fetal alcohol syndrome
Authors: Douglas Tania S. , Mutsvangwa Tinashe E.M. 
Published: January 2010

AbstractThe facial anomalies associated with fetal alcohol syndrome (FAS), some of which are also present in individuals with less severe forms of the broader category of fetal alcohol spectrum disorders (FASD), are typically identified with the aid of linear distance measurements taken between facial landmarks. Digital facial imaging methods are increasingly being used in syndrome delineation. Distance measurements derived from stereo‐photogrammetry and facial surface imaging have been used to study the FAS facial anomalies. Geometric morphometric methods capture the spatial arrangement between landmarks, providing a statistical platform for comparison of facial shapes, and have been shown to hold promise for characterizing the FAS facial shape. We review the progression in the use of imaging and image analysis methods in studies on the facial phenotype associated with FAS. © 2010 Wiley‐Liss, Inc.
Rubinstein–Taybi syndrome associated with Chiari type I malformation caused by a large 16p13.3 microdeletion: A contiguous gene syndrome?
Authors: Wójcik Cezary , Volz Kim , Ranola Maria , Kitch Karla , Karim Tariza , O'Neil Joseph , Smith Jodi , Torres‐Martinez Wilfredo 
Published: January 2010

AbstractRubinstein–Taybi Syndrome (RSTS, OMIM 180849) is a rare condition, which in 65% of cases is caused by haploinsufficiency of CREBBP (cAMP response element binding protein binding protein) localized to 16p13.3. A small subset of RSTS cases caused by 16p13.3 microdeletions involving neighboring genes have been recently suggested to be a true contiguous gene syndrome called severe RSTS or 16p13.3 deletion syndrome (OMIM 610543). In the present report, we describe a case of a 2‐year‐old female with RSTS who, besides most of the typical features of RSTS has corpus callosum dysgenesis and a Chiari type I malformation which required neurosurgical decompression. CGH microarray showed a ∼520.7 kb microdeletion on 16p13.3 involving CREBBP, ADCY9, and SRL genes. We hypothesize that the manifestations in this patient might be influenced by the haploinsufficiency for ADCY9 and SRL. © 2010 Wiley‐Liss, Inc.
Proteolytic Cleavage of Versican During Limb Joint Development
Authors: Capehart Anthony A. 
Published: January 2010

AbstractVersican is highly expressed in developing joint interzones during limb morphogenesis. This study was undertaken to examine whether proteolytic cleavage of versican occurs that could potentially impact its function during the process of embryonic synovial joint formation. Using an antibody to the DPEAAE neoepitope generated by ADAMTS proteolysis, versican amino terminal cleavage fragments were detected in joint interzones at 12–16 days post coitum (dpc). ADAMTS‐1 localization overlapped that of DPEAAE‐reactive versican fragments suggesting it as one possible protease activity involved in processing of versican in the interzone. Results show that increased cleavage of versican in the interzone accompanies cavitation and suggests that proteolytic modification of versican may be important during the process of synovial joint maturation. Anat Rec, 293:208–214, 2010. © 2010 Wiley‐Liss, Inc.
Management of nonresponse to rituximab in rheumatoid arthritis: Predictors and outcome of re‐treatment
Authors: Vital E. M. , Dass S. , Rawstron A. C. , Buch M. H. , Goëb V. , Henshaw K. , Ponchel F. , Emery P. 
Published: January 2010

AbstractObjectiveA proportion of patients with rheumatoid arthritis (RA) have disease that fails to respond to an initial cycle of rituximab. Using highly sensitive flow cytometry (HSFC), it has been shown that most patients who do not exhibit a response, as measured using the European League Against Rheumatism (EULAR) criteria, have persistent circulating B cell levels at week 2 after initial treatment with rituximab. This study was undertaken to examine whether an additional cycle of rituximab would improve B cell depletion and clinical response in patients whose disease did not respond to the initial cycle.MethodsPatients with RA (n = 158) were treated with a first cycle of rituximab (2 infusions of 1 gm each). Clinical responses were assessed using EULAR criteria, and patients were categorized as either first‐cycle responders or first‐cycle nonresponders. Baseline characteristics of first‐cycle nonresponders (n = 38) and first‐cycle responders (n = 65) with complete data were compared. First‐cycle nonresponders (n = 25) were treated with a second cycle of rituximab at least 6 months after the first cycle. HSFC was performed at baseline, immediately prior to the second infusion (week 2), 1 month after the second infusion (week 6), and then every 3 months for each cycle of rituximab. Complete B cell depletion was defined as being <0.0001 × 109 cells/liter.ResultsAt baseline, the number of preplasma cells was significantly higher in first‐cycle nonresponders than in first‐cycle responders (P = 0.003). Following the first infusion of the first cycle of rituximab, only 9% of first‐cycle nonresponders (3 of 34) exhibited complete depletion of B‐lineage cells, compared with 37% of first‐cycle responders (22 of 59) (P = 0.007). Following the first infusion of the second cycle of rituximab, 38% of first‐cycle nonresponders exhibited complete depletion. Twenty‐six weeks after the second cycle, there was a significant improvement in the Disease Activity Score in 28 joints, with 72% of patients exhibiting a EULAR response.ConclusionRA patients whose disease did not respond to an initial cycle of rituximab have higher circulating preplasma cell numbers at baseline and incomplete depletion. Our findings indicate that an additional cycle of rituximab administered prior to total B cell repopulation enhances B cell depletion and clinical responses.