The Experts below are selected from a list of 879 Experts worldwide ranked by ideXlab platform
Naomichi Matsumoto - One of the best experts on this subject based on the ideXlab platform.
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inv dup del 4 p14 p16 3 p16 3 qter with manifestations of partial duplication 4p and Wolf Hirschhorn Syndrome
American Journal of Medical Genetics Part A, 2003Co-Authors: Yuki Kondoh, Takaya Toma, Hirofumi Ohashi, Naoki Harada, Koichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi MatsumotoAbstract:An 8-year-old girl with a combination of clinical manifestations of partial duplication 4p and the Wolf–Hirschhorn Syndrome was studied. Chromosomal G-banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at 4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf–Hirschhorn Syndrome critical region). The chromosomes of the parents were normal. Her karyotype was thus 46,XX, inv dup del(4)(:p14 p16.3::p16.3 qter) de novo. The inverted duplication deletion was assumed to have arisen through chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a dicentric intermediate, breakage of the dicentric to result in a monocentric, and telomere capture/healing of the broken end. Olfactory receptor gene clusters at 4p16.3 were ruled out as an intermediary of the duplication deletion process. © 2003 Wiley-Liss, Inc.
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inv dup del 4 p14 p16 3 p16 3 qter with manifestations of partial duplication 4p and Wolf Hirschhorn Syndrome
American Journal of Medical Genetics Part A, 2003Co-Authors: Yuki Kondoh, Takaya Toma, Hirofumi Ohashi, Naoki Harada, Koichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi MatsumotoAbstract:An 8-year-old girl with a combination of clinical manifestations of partial duplication 4p and the Wolf-Hirschhorn Syndrome was studied. Chromosomal G-banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at 4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf-Hirschhorn Syndrome critical region). The chromosomes of the parents were normal. Her karyotype was thus 46,XX, inv dup del(4)(:p14 --> p16.3::p16.3 --> qter) de novo. The inverted duplication deletion was assumed to have arisen through chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a dicentric intermediate, breakage of the dicentric to result in a monocentric, and telomere capture/healing of the broken end. Olfactory receptor gene clusters at 4p16.3 were ruled out as an intermediary of the duplication deletion process.
Yuki Kondoh - One of the best experts on this subject based on the ideXlab platform.
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inv dup del 4 p14 p16 3 p16 3 qter with manifestations of partial duplication 4p and Wolf Hirschhorn Syndrome
American Journal of Medical Genetics Part A, 2003Co-Authors: Yuki Kondoh, Takaya Toma, Hirofumi Ohashi, Naoki Harada, Koichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi MatsumotoAbstract:An 8-year-old girl with a combination of clinical manifestations of partial duplication 4p and the Wolf–Hirschhorn Syndrome was studied. Chromosomal G-banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at 4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf–Hirschhorn Syndrome critical region). The chromosomes of the parents were normal. Her karyotype was thus 46,XX, inv dup del(4)(:p14 p16.3::p16.3 qter) de novo. The inverted duplication deletion was assumed to have arisen through chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a dicentric intermediate, breakage of the dicentric to result in a monocentric, and telomere capture/healing of the broken end. Olfactory receptor gene clusters at 4p16.3 were ruled out as an intermediary of the duplication deletion process. © 2003 Wiley-Liss, Inc.
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inv dup del 4 p14 p16 3 p16 3 qter with manifestations of partial duplication 4p and Wolf Hirschhorn Syndrome
American Journal of Medical Genetics Part A, 2003Co-Authors: Yuki Kondoh, Takaya Toma, Hirofumi Ohashi, Naoki Harada, Koichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi MatsumotoAbstract:An 8-year-old girl with a combination of clinical manifestations of partial duplication 4p and the Wolf-Hirschhorn Syndrome was studied. Chromosomal G-banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at 4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf-Hirschhorn Syndrome critical region). The chromosomes of the parents were normal. Her karyotype was thus 46,XX, inv dup del(4)(:p14 --> p16.3::p16.3 --> qter) de novo. The inverted duplication deletion was assumed to have arisen through chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a dicentric intermediate, breakage of the dicentric to result in a monocentric, and telomere capture/healing of the broken end. Olfactory receptor gene clusters at 4p16.3 were ruled out as an intermediary of the duplication deletion process.
Joris Vermeesch - One of the best experts on this subject based on the ideXlab platform.
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A microdeletion proximal of the critical deletion region is associated with mild Wolf-Hirschhorn Syndrome.
American journal of medical genetics. Part A, 2012Co-Authors: Femke Hannes, Peter Hammond, Oliver Quarrell, Jean-pierre Fryns, Koenraad Devriendt, Joris VermeeschAbstract:It is generally accepted that the facial phenotype of Wolf-Hirschhorn Syndrome is caused by deletions of either Wolf-Hirschhorn critical regions 1 or 2 (WHSCR 1-2). Here, we identify a 432 kb deletion located 600 kb proximal to both WHSCR1-2 in a patient with a WHS facial phenotype. Seven genes are underlying this deletion region including FAM193a, ADD1, NOP14, GRK4, MFSD10, SH3BP2, TNIP2. The clinical diagnosis of WHS facial phenotype was confirmed by 3D facial analysis using dense surface modeling. Our results suggest that the WHSCR1-2 flanking sequence contributes directly or indirectly to the severity of WHS. Sequencing the Wolf-Hirschhorn Syndrome candidate 1 and 2 genes did not reveal any mutations. Long range position effects of the deletion that could influence gene expression within the WHSCR were excluded in EBV cell lines derived from patient lymphoblasts. We hypothesize that either (1) this locus harbors regulatory sequences which affect gene expression in the WHSCR1-2 in a defined temporal and spatial developmental window or (2) that this locus is additive to deletions of WHSCR1-2 increasing the phenotypic expression.
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fine grained facial phenotype genotype analysis in Wolf Hirschhorn Syndrome
European Journal of Human Genetics, 2012Co-Authors: Peter Hammond, Susan Parekh, Michael Suttie, Francesca Forzano, Francesca Faravelli, Femke Hannes, Koen Devriendt, Steve Williams, Joris Vermeesch, Dominic J. McmullanAbstract:Wolf–Hirschhorn Syndrome is caused by anomalies of the short arm of chromosome 4. About 55% of cases are due to de novo terminal deletions, 40% from unbalanced translocations and 5% from other abnormalities. The facial phenotype is characterized by hypertelorism, protruding eyes, prominent glabella, broad nasal bridge and short philtrum. We used dense surface modelling and pattern recognition techniques to delineate the milder facial phenotype of individuals with a small terminal deletion (breakpoint within 4p16.3) compared to those with a large deletion (breakpoint more proximal than 4p16.3). Further, fine-grained facial analysis of several individuals with an atypical genotype and/or phenotype suggests that multiple genes contiguously contribute to the characteristic Wolf–Hirschhorn Syndrome facial phenotype.
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duplication of the Wolf Hirschhorn Syndrome critical region causes neurodevelopmental delay
European Journal of Medical Genetics, 2010Co-Authors: Femke Hannes, Joris Vermeesch, Malgorzata Drozniewska, Olga HausAbstract:Abstract Wolf-Hirschhorn Syndrome (WHS) is caused by deletions on chromosome 4p and is clinically well defined. Genotype-phenotype correlations of patients with WHS point to a critical locus to be responsible for the main characteristics of this disorder. Submicroscopic duplications of this region, however, are not known. Here we report a patient with an interstitial 560 kb duplication overlapping this critical locus. The present case shows that not only deletions but also duplications of the Wolf-Hirshhorn critical region cause mental retardation and multiple congenital anomalies. Interestingly, the duplication phenotype overlaps partially with the deletion phenotype. However, his facial phenotype differs from the typical WHS gestalt.
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Wolf Hirschhorn Syndrome facial dysmorphic features in a patient with a terminal 4p16 3 deletion telomeric to the whscr and whscr 2 regions
European Journal of Human Genetics, 2009Co-Authors: Hannelie M Engbers, Joris Vermeesch, Jasper J Van Der Smagt, Ruben Van T Slot, Ron Hochstenbach, Martin PootAbstract:We report on a patient with developmental delay and several facial characteristics reminiscent of Wolf–Hirschhorn Syndrome, who carries a terminal 4p16.3 deletion of minimally 1.691 Mb and maximally 1.698 Mb. This deletion contains the FGFRL1 gene, but does not include the WHSC1 gene. Given its expression pattern and its involvement in bone and cartilage formation during embryonic development, the FGFRL1 gene represents a plausible candidate gene for part of the facial characteristics of Wolf–Hirshhorn Syndrome in 4p16.3 deletion patients.
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pathogenic significance of deletions distal to the currently described Wolf Hirschhorn Syndrome critical regions on 4p16 3
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2008Co-Authors: Sarah T South, Femke Hannes, Joris Vermeesch, Gene S Fisch, Marcella ZollinoAbstract:Within recent years, numerous individuals have been identified with terminal 4p microdeletions distal to the currently described critical regions for the Wolf-Hirschhorn Syndrome (WHS). Some of these individuals do not display features consistent with WHS whereas others have a clinical phenotype with some overlap to the WHS phenotype. In this review we discuss the genetic and clinical presentation of these cases in an attempt to understand the consequence of monosomy of the genes distal to the proposed critical regions and identify the distal boundary for pathogenic genes involved in components of the WHS phenotype.
Marcella Zollino - One of the best experts on this subject based on the ideXlab platform.
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international meeting on Wolf Hirschhorn Syndrome update on the nosology and new insights on the pathogenic mechanisms for seizures and growth delay
American Journal of Medical Genetics Part A, 2020Co-Authors: Julian Nevado, Marcella Zollino, Jacobo Limeres, Raquel Blanco, Cesar Cobaleda, Christelle Golzio, Isabelle Beaudrybellefeuille, Sarah Berrocoso, Pilar Barruz, Candela SerranomartinAbstract:"An International Meeting on Wolf-Hirschhorn Syndrome (WHS)" was held at The University Hospital La Paz in Madrid, Spain (October 13-14, 2017). One hundred and twenty-five people, including physicians, scientists and affected families, attended the meeting. Parent and patient advocates from the Spanish Association of WHS opened the meeting with a panel discussion to set the stage regarding their hopes and expectations for therapeutic advances. In keeping with the theme on therapeutic development, the sessions followed a progression from description of the phenotype and definition of therapeutic endpoints, to definition of genomic changes. These proceedings will review the major points of discussion.
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oligonephronia and Wolf Hirschhorn Syndrome a further observation
American Journal of Medical Genetics Part A, 2018Co-Authors: Antonio Gatto, Marcella Zollino, Pietro Ferrara, Chiara Leoni, Roberta Onesimo, Francesco Emma, Giuseppe ZampinoAbstract:Wolf-Hirschhorn Syndrome (WHS) is a rare chromosomal disorder caused by a partial deletion of chromosome 4 (4p16.3p16.2). We describe a case of a male 9 years old children with WHS proteinuria and hypertension. Laboratory data showed creatinine 1.05 mg/dl, GFR 65.9 ml/min/1.73 m2 , cholesterol 280 mg/dl, triglyceride 125 mg/dl with electrolytes in the normal range. Urine collection showed protein 2.72 g/L with a urine protein/creatinine ratio (UP /UCr ratio) of 4.2 and diuresis of 1,100 ml. Renal ultrasound showed reduced kidney dimensions with diffusely hyperechogenic cortex and poorly visualized pyramids. Renal biopsy showed oligonephronia with focal segmental glomerulosclerosis associated with initial tubulointerstitial sclerotic atrophy. The child began therapy with Angiotensin-converting enzyme inhibitors (ACE-inhibitors) to reduce proteinuria and progression of chronic kidney disease. In the literature the anomalies of number of glomeruli oligonephronia and oligomeganephronia (OMN) are described in two forms, one without any associated anomalies, sporadic, and solitary and the other with one or more anomalies. Our review of the literature shows that the pathogenesis of this anomaly is unknown but the role of chromosome 4 is very relevant. Many cases of OMN are associated with anomalies on this chromosome, in the literature cases series we observed this association in 14/48 cases (29.2%) and in 7 of these 14 cases with WHS. Our case and the review of literature demonstrate how periodic urinalysis and renal ultrasound monitoring is recommended in patients affected by WHS and the renal biopsy must be performed when there is the onset of proteinuria.
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ocular manifestations in Wolf Hirschhorn Syndrome
Journal of Aapos, 2009Co-Authors: Anna Dickmann, Rosa Parrilla, Annabella Salerni, Gustavo Savino, Isabella Vasta, Marcella Zollino, Sergio Petroni, Giuseppe ZampinoAbstract:Introduction Wolf-Hirschhorn Syndrome (WHS) multiple congenital anomalies/mental retardation is caused by partial deletion of the short arm of chromosome 4 and can be considered a contiguous gene Syndrome, characterized by typical facial appearance, mental retardation, growth delay, and seizures. Methods We investigated the ocular defects in a population of 10 patients with WHS and analyzed the relationship between ocular findings and the extent of deletion on chromosome 4. Results The ocular abnormalities found included hypertelorism, strabismus, refractive errors, epicanthal folds, proptosis, downslanting palpebral fissures, microphthalmos, microcornea, iris coloboma, optic nerve coloboma, ocular cyst, ptosis, glaucoma, and nystagmus. Different breakpoints of the chromosomal rearrangement were observed in individual patients, ranging from 4p15.1 to 4p16.3, and the size of chromosomal deletion ranged from 2.6 to 26 million base pairs. Conclusions Congenital glaucoma and colobomatous ocular cysts have rarely been described in WHS patients that were previously reported. In all cases exhibiting strabismus, an exodeviation was present. Comparing genotype with ocular phenotype, a relationship between the size of deletion and the severity of the ocular involvement was observed in all cases but one.
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pathogenic significance of deletions distal to the currently described Wolf Hirschhorn Syndrome critical regions on 4p16 3
American Journal of Medical Genetics Part C-seminars in Medical Genetics, 2008Co-Authors: Sarah T South, Femke Hannes, Joris Vermeesch, Gene S Fisch, Marcella ZollinoAbstract:Within recent years, numerous individuals have been identified with terminal 4p microdeletions distal to the currently described critical regions for the Wolf-Hirschhorn Syndrome (WHS). Some of these individuals do not display features consistent with WHS whereas others have a clinical phenotype with some overlap to the WHS phenotype. In this review we discuss the genetic and clinical presentation of these cases in an attempt to understand the consequence of monosomy of the genes distal to the proposed critical regions and identify the distal boundary for pathogenic genes involved in components of the WHS phenotype.
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the new Wolf Hirschhorn Syndrome critical region whscr 2 a description of a second case
American Journal of Medical Genetics Part A, 2005Co-Authors: Laura Rodriguez, Marcella Zollino, Salvador Climent, Elena Mansilla, Fermina Lopezgrondona, Maria Luisa Martinezfernandez, Marina Murdolo, Maria Luisa MartinezfriasAbstract:The Wolf-Hirschhorn Syndrome (WHS), is a well known contiguous gene Syndrome characterized by microcephaly, hypertelorism, prominent glabella, epicanthal folds, cleft lip or palate, cardiac defects, growth and mental retardation and seizures. The currently accepted WHS critical region (WHSCR) is localized between the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical manifestations of the Syndrome. Here we present a patient with a subtelomeric deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial appearance and two episodes of seizures in conjunction with fever. The high-resolution G-banded karyotype was normal. Fluorescence in situ hybridization (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this patient was from the D4S3327 to the telomere, enabling the size of the deletion to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient supports the recent proposal by Zollino et al. [2003] that the critical region for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98-D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].
Koichiro Yoshiura - One of the best experts on this subject based on the ideXlab platform.
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inv dup del 4 p14 p16 3 p16 3 qter with manifestations of partial duplication 4p and Wolf Hirschhorn Syndrome
American Journal of Medical Genetics Part A, 2003Co-Authors: Yuki Kondoh, Takaya Toma, Hirofumi Ohashi, Naoki Harada, Koichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi MatsumotoAbstract:An 8-year-old girl with a combination of clinical manifestations of partial duplication 4p and the Wolf–Hirschhorn Syndrome was studied. Chromosomal G-banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at 4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf–Hirschhorn Syndrome critical region). The chromosomes of the parents were normal. Her karyotype was thus 46,XX, inv dup del(4)(:p14 p16.3::p16.3 qter) de novo. The inverted duplication deletion was assumed to have arisen through chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a dicentric intermediate, breakage of the dicentric to result in a monocentric, and telomere capture/healing of the broken end. Olfactory receptor gene clusters at 4p16.3 were ruled out as an intermediary of the duplication deletion process. © 2003 Wiley-Liss, Inc.
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inv dup del 4 p14 p16 3 p16 3 qter with manifestations of partial duplication 4p and Wolf Hirschhorn Syndrome
American Journal of Medical Genetics Part A, 2003Co-Authors: Yuki Kondoh, Takaya Toma, Hirofumi Ohashi, Naoki Harada, Koichiro Yoshiura, Tohru Ohta, Tatsuya Kishino, Norio Niikawa, Naomichi MatsumotoAbstract:An 8-year-old girl with a combination of clinical manifestations of partial duplication 4p and the Wolf-Hirschhorn Syndrome was studied. Chromosomal G-banding and FISH analyses showed a 33.2-Mb segment of inverted duplication at 4p14-p16.3 and a 2.8-Mb segment of deletion at 4p16.3-pter (including the Wolf-Hirschhorn Syndrome critical region). The chromosomes of the parents were normal. Her karyotype was thus 46,XX, inv dup del(4)(:p14 --> p16.3::p16.3 --> qter) de novo. The inverted duplication deletion was assumed to have arisen through chromatid breakage at 4p16.3, U-type reunion at the breakpoints to produce a dicentric intermediate, breakage of the dicentric to result in a monocentric, and telomere capture/healing of the broken end. Olfactory receptor gene clusters at 4p16.3 were ruled out as an intermediary of the duplication deletion process.
