oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
Chromosome 12q24.31-q24.33 deletion causes multiple dysmorphic features and developmental delay: First mosaic patient and overview of the phenotype related to 12q24qter defects
Jawaher Al-Zahrani, Naji Al-Dosari, Nada AbuDheim, Tarfa A Alshidi, Dilek Colak, Ola Al-Habit, Ali Al-Odaib, Nadia Sakati, Brian Meyer, Pinar T Ozand, Namik Kaya
Molecular Cytogenetics , 2011, DOI: 10.1186/1755-8166-4-9
Abstract: We have clinically screened more than 100 patients with dysmorphic features, mental retardation and normal karyotype using high density oligo array-CGH (aCGH) and identified a ~9.2 Mb hemizygous interstitial deletion at the 12q telomere (Chromosome 12: 46,XY,del(12)(q24.31q24.33) in a severely developmentally retarded patient having dysmorphic features such as low set ears, microcephaly, undescended testicles, bent elbow, kyphoscoliosis, and micropenis. Parents were found to be not carriers. MLPA experiments confirmed the aCGH result. Interphase FISH revealed mosaicism in cultured peripheral blood lymphocytes.Since conventional G-Banding technique missed the abnormality; this work re-confirms that any child with unexplained developmental delay and systemic involvement should be studied by aCGH techniques. The FISH technique, however, would still be useful to further delineate the research work and identify such rare mosaicism. Among the 52 deleted genes, P2RX2, ULK1, FZD10, RAN, NCOR2 STX2, TESC, FBXW8, and TBX3 are noteworthy since they may have a role in observed phenotype.Genomic imbalances certainly are major causes of congenital and developmental abnormalities. These include dysmorphia, mental retardation, developmental delay, and multiple congenital anomalies. Some of these genetic anomalies causing such phenotypes can be various and some of these are associated to telomeric/subtelomeric deletions. Among these chromosome 12q24.31-q24.33 telomeric/subtelomeric deletions are rare and only a few patients have been reported previously [1-3]; interestingly none of these were mosaic. Some attempts were made to establish phenotype-genotype correlation [1], no clear relationship could be found. Genes such as RAN, P2RX2, FZD10, and ULK1 were mentioned as likely candidate genes implicated in the clinical features of the patients reported [1]. In this report a detailed clinical description and molecular cytogenetics analysis of a patient with de novo 12q interstitial del
Mosaicism for combined tetrasomy of chromosomes 8 and 18 in a dysmorphic child: A result of failed tetraploidy correction?
Gunnar Houge, Helle Lyb?k, Sasha Gulati
BMC Medical Genetics , 2009, DOI: 10.1186/1471-2350-10-42
Abstract: In a markedly dysmorphic child with heart malformations and developmental delay, CGH analysis of newborn blood DNA suggested a 50% dose increase of chromosomes 8 and 18, despite a normal standard karyotype investigation. Subsequent FISH analysis revealed leukocytes with four chromosomes 8 and four chromosomes 18. The child's phenotype had resemblance to both mosaic trisomy 8 and mosaic trisomy 18. The double tetrasomy was caused by mitotic malsegregation of all four chromatids of both chromosome pairs. A possible origin of such an error is incomplete correction of a tetraploid state resulting from failed cytokinesis or mitotic slippage during early embryonic development.This unique case suggests that embryonic cells may have a mechanism for tetraploidy correction that involves mitotic pairing of homologous chromosomes.Unlike meiotic non-disjunctions, mitotic non-disjunctions are rarely observed in humans with the exception of mosaicism for trisomy 8, 9 or 20 [1,2]. In some cases mosaic trisomy of more than one chromosome have been seen [3]. Such mosaic variegated aneuploidy is due to mitotic errors, often associated with premature centromere division [4]. In contrast to mosaic trisomies, the finding of mosaic whole-chromosome tetrasomy is without precedence. Here we present such a patient; a dysmorphic newborn child with mosaicism of leukocytes containing 50 chromosomes due to tetrasomy of chromosomes 8 and 18. This unique clinical case may have relevance concerning the origin of aneuploidy in cancer [5-8] because it indirectly suggests that there might be a mechanism for tetraploidy correction during fetal development that involves mitotic pairing of homologous chromosomes.A baby girl was delivered by cesarean section in week 36 due to maternal hypertension with mild preeclampsia, birth weight 2910 g, length 47 cm. Polyhydramnios was detected at the end of the pregnancy. She had persistent ductus arteriosus (PDA), a small muscular-type ventricle septal defect (VSD)
Trisomy 13 mosaicism demonstrated only in skin fibroblasts in a patient presenting psychomotor retardation, pigmentary dysplasia and some dysmorphic features
Ferreira, A.P.S.;Mazzucatto, L.F.;Ramos, E.S.;Pina-Neto, J.M.;
Brazilian Journal of Genetics , 1996, DOI: 10.1590/S0100-84551996000400023
Abstract: a brazilian female infant presented delayed psychomotor development, skin pigmentary dysplasia and some dysmorphic features. chromosome analysis from peripheral blood culture was normal, but the karyotype from skin fibroblasts revealed mosaicism for trisomy 13. this case demonstrates the relevance of performing chromosomal analysis of skin fibroblasts in patients with mental retardation, associated with pigmentary dysplasia of the skin and a normal karyotype in peripheral blood lymphocytes. to our knowledge, it is the first report of trisomy 13 demonstrated only in skin fibroblasts.
Analphoid supernumerary marker chromosome characterized by aCGH and FISH as inv dup(3)(q25.33qter) de novo in a child with dysmorphic features and streaky pigmentation: case report
Sabita K Murthy, Ashok K Malhotra, Preenu S Jacob, Sehba Naveed, Eman EM Al-Rowaished, Sara Mani, Shabeer Padariyakam, R Pramathan, Ravi Nath, Mahmoud Al-Ali, Lihadh Al-Gazali
Molecular Cytogenetics , 2008, DOI: 10.1186/1755-8166-1-19
Abstract: We describe here a one month old female child with several dysmorphic features and with a de novo analphoid supernumerary marker chromosome only in cultured skin fibroblast cells and not in lymphocytes. The marker was characterized as analphoid inversion-duplication 3q25.33-qter by oligo array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH) studies. The final skin fibroblast karyotype was interpreted as 47,XX,+der(3).ish inv dup(3)(qter-q25.33::q25.33-qter)(subtel 3q+,subtel 3q+) de novo.In addition to the eight reported cases of analphoid inversion-duplication 3q supernumerary marker in the literature, this is yet another case of 3q sSMC with a new breakpoint at 3q25.33 and with varying phenotype as described in the case report. Identification of more and more similar cases of analphoid inversion-duplication 3q marker will help in establishing a better genotype-phenotype correlation. The study further demonstrates that aCGH in conjunction with routine cytogenetics and FISH is very useful in precisely identifying and characterizing a marker chromosome, and more importantly help in providing with an accurate genetic diagnosis and better counseling to the family.Small supernumerary marker chromosomes occur in 0.075% of unselected prenatal cases and in 0.044% of consecutively studied postnatal cases, and majority of them are de novo in origin [1-4]. Phenotype of individuals with de novo sSMC vary from normal to extremely mild or severe, depending on the chromosomal region involved and the euchromatic content present [5-7]. Although a number of reports describe the occurrence of a variety of sSMC for nearly all the chromosomes, the number for each type is not large enough to suggest a good genotype-phenotype correlation for a given sSMC, except for inv dup(15) and inv dup(22) where the phenotypic consequences are well described [6,8-10]. We describe here the phenotype and corresponding molecular cytogenetic results of a child with
A 54 Mb 11qter duplication and 0.9 Mb 1q44 deletion in a child with laryngomalacia and agenesis of corpus callosum
Meena Lall, Seema Thakur, Ratna Puri, Ishwar Verma, Mithali Mukerji, Pankaj Jha
Molecular Cytogenetics , 2011, DOI: 10.1186/1755-8166-4-19
Abstract: We report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1)t(1;11)(q44;q14)pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11)(q44;q14). SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter.Laryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region.Partial Trisomy 11q syndrome is a rare disorder with defined clinical features and has been documented in the list of rare syndromes by National Organization of Rare Disorders (NORD), USA http://www.raredisease.org webcite[1]. These clinical features consist of distinct pattern of facial features, mental retardation, pre- and postnatal growth retardation, hypotonia, congenital heart defects and limb malformations [1-3]. There is one report [4], which states that the malformation of the upper airway is associated with trisomy 11q.Deletion 1q44 syndrome is a well-recognized syndrome archived in the National Medical Library http:/ / www.nlm.nih.gov/ archive/ 20061212/ mesh/ jablonski/ mesh/ jablonski/ syndrome_db.html webcite[5]. The clinical features of 1qter syndrome include short stature, developmental delay, mental retardation, microcephaly, seizures, an abnormal corpus callosum ranging from partial to complete agenesis, and abnormal ear sh
A Case of 17q21.31 Microduplication and 7q31.33 Microdeletion, Associated with Developmental Delay, Microcephaly, and Mild Dysmorphic Features  [PDF]
Adrian Mc Cormack,Juliet Taylor,Leah Te Weehi,Donald R. Love,Alice M. George
Case Reports in Genetics , 2014, DOI: 10.1155/2014/658570
Abstract: Concurrent cryptic microdeletion and microduplication syndromes have recently started to reveal themselves with the advent of microarray technology. Analysis has shown that low-copy repeats (LCRs) have allowed chromosome regions throughout the genome to become hotspots for nonallelic homologous recombination to take place. Here, we report a case of a 7.5-year-old girl who manifests microcephaly, developmental delay, and mild dysmorphic features. Microarray analysis identified a microduplication in chromosome 17q21.31, which encompasses the CRHR1, MAPT, and KANSL1 genes, as well as a microdeletion in chromosome 7q31.33 that is localised within the GRM8 gene. To our knowledge this is one of only a few cases of 17q21.31 microduplication. The clinical phenotype of patients with this microduplication is milder than of those carrying the reciprocal microdeletions, and suggests that the lower incidence of the former compared to the latter may be due to underascertainment. 1. Introduction Since the advent of microarray technology considerable progress has been made in identifying small scale chromosome imbalances. The existence of colocalized microdeletion and microduplication syndrome sites has come to the fore in the recent years and a significant number of new microduplication syndromes have emerged such as 17p11.2 [1] and 22q11.21 [2]. These syndromes, like the corresponding microdeletion syndromes at these locations, appear to be driven by nonallelic homologous recombination (NAHR) involving low-copy repeats (LCRs or segmental duplications) [3–8]. LCRs are DNA fragments greater than 1?Kb in size, have 90% DNA sequence homology, and are thought to account for approximately 3–10% of the total genome. The MAPT gene located on chromosome 17q21.31 is flanked by LCRs and two extended haplotypes, designated H1 and H2, have been identified [9, 10]. The H2 haplotype is a 900?kb inversion polymorphism that has been reported as the likely ancestral state and which has a tendency to undergo recombination [11] leading to the 17q21.31 microdeletion syndrome. This syndrome has been well characterised and appears to be caused by haploinsufficiency of at least one gene, KANSL, within the deleted region [12, 13]. The more common H1 haplotype appears to be overrepresented in patients manifesting progressive supranuclear palsy [14]. Here, we report a 7.5-year-old girl with a 647?kb duplication involving interstitial chromosome region 17q21.31 as well as a 232?kb heterozygous interstitial deletion involving chromosome region 7q31.33. We review this case in conjunction with
Microdeletion of 6q16.1 encompassing EPHA7 in a child with mild neurological abnormalities and dysmorphic features: case report
Ryan N Traylor, Zheng Fan, Beth Hudson, Jill A Rosenfeld, Lisa G Shaffer, Beth S Torchia, Blake C Ballif
Molecular Cytogenetics , 2009, DOI: 10.1186/1755-8166-2-17
Abstract: We report a 16-month-old male presenting with developmental delay and dysmorphic features who was found by array-based comparative genomic hybridization (aCGH) to have a ~2.16 Mb de novo deletion within chromosome band 6q16.1 that encompasses only two genes. Expression studies of the mouse homologue of one of the genes, the ephrin receptor 7 gene (EPHA7), have shown the gene functions during murine embryogenesis to form cortical domains, determine brain size and shape, and play a role in development of the central nervous system (CNS).Our results suggest that deletion of EPHA7 plays a role in the neurologic and dysmorphic features, including developmental delay, hypotonia, and ear malformations, observed in some 6q deletion patients.Conventional cytogenetic analyses have identified fewer than 100 individuals with constitutional deletions within 6q. A review by Hopkin et al. [1] of 57 previously reported 6q deletion cases characterized cytogenetically attempted to organize phenotype/karyotype correlations into three phenotypic groups. Deletions within 6q11 to 6q16, designated Group A, showed a high incidence of hernias, upslanting palpebral fissures, and thin lips with a lower frequency of microcephaly, micrognathia, and heart malformations. Group B deletions spanned 6q15-6q25 and showed increased intrauterine growth retardation, abnormal respiration, hypertelorism, and upper limb malformations. Group C comprised deletions in 6q25 to 6qter, which presented with retinal abnormalities, cleft palate, and genital hypoplasia. Mental retardation was the only finding common among all cases of 6q deletion. The three groups also shared ear anomalies, hypotonia, and postnatal growth retardation in 90%, 82%, and 68% of cases, respectively [1].Since the Hopkin et al. [1] review, 10 individuals with deletions encompassing 6q16.1 identified using aCGH have been reported [2-7]. Features seen among these cases are varied as the sizes of these deletions span 6–34 Mb within 6q. Here,
A review on microcephaly genes  [PDF]
Shahid S.,Irshad S.
Biopolymers and Cell , 2012,
Abstract: This review aims to summarize the recent findings regarding microcephaly genes. We have discussed the molecular genetics studies of microcephaly genes including a comprehensive appraisal of the seven mapped loci (MCPH1–MCPH7), their corresponding genes and protein products of the genes, their likely role in normal brain development and the details of the mutations reported in these genes.
Body Dysmorphic Disorder  [PDF]
Perihan Cam Ray,Mehmet Emin Demirkol,Lut Tamam
Psikiyatride Guncel Yaklasimlar , 2012,
Abstract: Body dysmorphic disorder is a type of mental illness, wherein the affected person is concerned with body image, manifested as excessive concern about and preoccupation with a perceived defect of their physical features. Although it is a common disease and has been defined in the literature over a century, it is not a well known disease. Chronic, treatment resistant and sometimes delusional nature could result in severe functional impairment. The diagnosis and appropriate therapy of disorder are crucial because of increased suicidality and reduction in life quality. In this article the symptoms, etiology, clinical features and treatment of body dysmorphic disorder are briefly reviewed.
Chromosomal mosaicism goes global
Ivan Y Iourov, Svetlana G Vorsanova, Yuri B Yurov
Molecular Cytogenetics , 2008, DOI: 10.1186/1755-8166-1-26
Abstract: Chromosomal mosaicism was originally defined as the presence of cells differing with respect to their chromosome complement in the same individual [1]. Although chromosomal mosaicism is repeatedly registered during cytogenetic analysis, one of the commonest genetic tests in medical genetics [2], its significance remains usually underappreciated. Nonetheless, during the last decade, a growing amount of studies has demonstrated that chromosomal mosaicism does contribute to human diversity [3-7], diseases [2,4,5,7-12], early prenatal brain development [3,13], and aging [14]. However, the real biomedical meaning of chromosomal mosaicism in humans is hardly known.One of the previous studies published in Molecular Cytogenetics [15] has brought evidences that chromosomal mosaicism plays a role in the generation of meiotic aneuploidy known to be the leading genetic cause of human prenatal death and congenital malformations/learning disabilities [4,5,16]. Studying chromosome 21 in ovarian cells of normal female foetuses, Prof. Maj Hulten and her colleagues were able to give experimental support for their original hypothesis suggesting meiotic aneuploidy in human conceptuses to be the result of ovarian germline mosaicism that is produced during the normal prenatal development [15]. The data fit well with current concepts in biology of aneuploidy, essentially drawn from studies of trisomy 21 (Down's syndrome) [16]. More specifically, these findings have the potential to explain maternal age effect, recurrence of aneuploidy at subsequent conceptions, and abnormal maternal recombination patterns previously found via linkage analyses [15]. Although the idea put forward in this article has revolutionized our thinking about maternal meiotic aneuploidy suggesting mitotic aneuploidy to lie at the origin of meiotic aneuploidy, there was a strong experimental background for this hypothesis. Firstly, it has been recently noticed that chromosomal mosaicism is frequent among human foetuse
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.