• So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. (eur.nl)
  • Direct sequence analysis of the EHMT1 gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic EHMT1 mutation. (eur.nl)
  • Conclusions: The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. (eur.nl)
  • The spectrum of speculations regarding which gene might be responsible for such phenotype ranges from single gene haploinsufficiency to deletion of a cluster of immunogenes located distally to 18q21. (nih.gov)
  • Distal monosomy 10p is a rare chromosomal disorder in which the tip of the short arm (p arm) of chromosome 10 is deleted resulting in a variable phenotype depending on the size of the deletion. (orpha.net)
  • Haploinsufficiency for the trans-acting T-cell-specific transcription factor GATA-3 (encoded by the GATA3 gene, and mapped to the 10p14-pter region) is responsible for this phenotype. (orpha.net)
  • The differential diagnosis for patients with distal monosomy 10p should include deletion 22q11 syndrome and other causes of hypoparathyroidism, depending on the phenotype. (orpha.net)
  • Terminal 6q deletions cause a common but highly variable phenotype. (biomedcentral.com)
  • As these deletions are rare, there is only limited information about their effect on the clinical phenotype. (biomedcentral.com)
  • In Cri-Du-Chat syndrome (5p deletion), the genetic basis of the phenotype is haploinsufficiency for the telomerase reverse transcriptase gene ( TERT ), which is included in the deleted part of chromosome 5. (dorak.info)
  • In the rare disease erythropoietic protoporphyria , haploinsufficiency for ferrochelatase ( FECH ) contributes to the clinical phenotype but is not the only reason for the disease expression. (dorak.info)
  • TBX1 and CRKL haploinsufficiency is thought to cause the cardiac phenotype of the 22q11.2 deletion syndrome. (biomedcentral.com)
  • The TBX1 gene, a member of a phylogenetically conserved T-box gene family of DNA-binding transcription factors, is mapped to the 22q11.2, and is hypothesised to be responsible for the cardiac phenotype of 22q11.2 deletion syndrome. (biomedcentral.com)
  • When this situation engenders a dominant phenotype we speak of haploinsufficiency (HI). (biomedcentral.com)
  • We have been studying the molecular basis of the phenotype of individuals with large deletions of chromosome 18q. (psu.edu)
  • These individuals were diagnosed by conventional cytogenetic methods, and interstitial deletions including only the proximal part of 6q27 were also considered to be terminal. (biomedcentral.com)
  • To our knowledge, this is one of the smallest interstitial deletions in the chromosome 22q11.2 region to be published to date. (jcpres.com)
  • Df1 /+ mice have a multi-gene deletion analogous to the chromosomal microdeletion that causes human 22q11.2DS, and like human 22q11.2DS patients exhibit high rates of hearing loss arising primarily from susceptibility to middle ear inflammation. (biorxiv.org)
  • Deletion of chromosomal locus 22q11.2 is associated with both schizophrenia and hearing loss in humans. (biorxiv.org)
  • The pathogenic germline deletion of varying lengths of chromosomal material along the short arm of chromosome 11, including WT1 and PAX6 , is the underlying defect. (medscape.com)
  • The deletion of varying lengths of chromosomal material along the short arm of chromosome 11 is the underlying defect, and developmental abnormalities are related to the contiguous loss of neighboring genes. (medscape.com)
  • Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. (dspace-express.com)
  • 2q37 deletion syndrome is a condition that can affect many parts of the body. (medlineplus.gov)
  • Most babies with 2q37 deletion syndrome are born with weak muscle tone (hypotonia), which usually improves with age. (medlineplus.gov)
  • Unusual physical features are also common in people with 2q37 deletion syndrome. (medlineplus.gov)
  • Other features of 2q37 deletion syndrome can include seizures and an inflammatory skin disorder called eczema. (medlineplus.gov)
  • A few people with 2q37 deletion syndrome develop a rare form of kidney cancer called Wilms tumor . (medlineplus.gov)
  • 2q37 deletion syndrome appears to be a rare condition, although its exact prevalence is unknown. (medlineplus.gov)
  • Researchers are working to identify all of the genes whose loss contributes to the features of 2q37 deletion syndrome. (medlineplus.gov)
  • While the deleted segment in 2q37 deletion syndrome varies in size, it always contains the HDAC4 gene. (medlineplus.gov)
  • Additionally, a few people with mutations in only the HDAC4 gene have many of the features of 2q37 deletion syndrome. (medlineplus.gov)
  • Most cases of 2q37 deletion syndrome are not inherited. (medlineplus.gov)
  • Background: The 9q subtelomeric deletion syndrome (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. (eur.nl)
  • The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene. (eur.nl)
  • Patients with 22q11.2 Deletion Syndrome (22q11.2DS) have a 25-30% risk of developing schizophrenia, and also suffer frequent hearing loss. (biorxiv.org)
  • In the Df1 /+ mouse model of human 22q11.2 Deletion Syndrome, we find that hearing loss shapes measures that are considered schizophrenia-relevant endophenotypes, such as central auditory gain and auditory sensorimotor gating. (biorxiv.org)
  • Among rare diseases, the KANSL1 haploinsufficiency syndrome is one of the most common conditions. (bmj.com)
  • Autoimmune disorders, IgA deficiency, and allergies seem to be common among individuals with 18q deletion syndrome [OMIM 601808]. (nih.gov)
  • Deletion of the PAX6 gene as part of the band 11p13 deletion in patients with AGR or WAGR syndrome results in aniridia. (medscape.com)
  • In hypermobility type of Ehlers-Danlos syndrome , haploinsufficiency (where one copy is unable to produce the protein in sufficient quantity) due to a 30-kb deletion of tenascin-X (TNXB) gene is responsible for the disease. (dorak.info)
  • Caused by a heterozygous multi-gene deletion, 22q11.2 deletion syndrome (22q11DS) is a relatively common genetic disorder (1:4000 live births). (biomedcentral.com)
  • Molecular Karyotyping in Anorectal Malformations: Could DGCR6 Gene Haploinsufficiency Cause Anal Atresia in 22q11 Deletion Syndrome? (jcpres.com)
  • [ 9 ] Approximately 10-12% of patients with Rubinstein-Taybi syndrome have deletions of CBP , and a smaller percentage have complex cytogenetic rearrangements involving the region of chromosome 16p that contains the gene. (medscape.com)
  • T Cell Transcriptome in Chromosome 22q11.2 Deletion Syndrome. (cdc.gov)
  • Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. (dspace-express.com)
  • Terminal 6q deletions are a variable group of chromosome disorders, with the largest deletions extending from 6q25.2 to 6qter (up to 16 Mb in size) and the smallest deletions restricted to the most distal band 6q27 (as small as 390 kb in size) [ 1 ]. (biomedcentral.com)
  • Deletions ranged between 248 and 482 kb in size and all distal breakpoints clustered within a complex 144 kb palindrome situated 75 kb upstream of SRRM2. (ox.ac.uk)
  • More importantly, although chromosome deletions are more frequent than KANSL1 mutations, we observed that KANSL1 is the major gene for this condition. (bmj.com)
  • The aim of the study was to screen the mutation of TBX1 and CRKL in isolated CTDs Chinese patients without 22q11.2 deletion and identify the pathomechanism of the missense mutations. (biomedcentral.com)
  • Strikingly diverse functional abnormalities have been identified for disease-linked ATP1A2 mutations which frequently lead to changes in the enzyme's voltage-dependent properties, kinetics, or apparent cation affinities, but some mutations are truly deleterious for enzyme function and thus cause full haploinsufficiency. (frontiersin.org)
  • No major phenotypic differences are noted between patients with large deletions and those with point mutations. (medscape.com)
  • The relatively low percentage (20%) of patients without deletions who have demonstrable mutations involving CBP may be due to an inability to identify all alterations that could be present in the gene or in its upstream or downstream regulatory regions. (medscape.com)
  • Therefore, the use of 5 cosmids covering the entire gene for fluorescence in situ hybridization (FISH) in order to identify more proximal deletions is recommended. (medscape.com)
  • Molecular analysis of 20 patients with 2q37.3 monosomy: definition of minimum deletion intervals for key phenotypes. (medlineplus.gov)
  • Interestingly, five of six patients who had reached adulthood had developed severe psychiatric pathology, which may indicate that EHMT1 haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect. (eur.nl)
  • We aimed to determine the prevalence, mechanism, and genetic background of autoimmunity, immune deficiency, and allergy in a cohort of patients with 18q deletions. (nih.gov)
  • Microarray oligonucleotide comparative genomic hybridization (aCGH) (Agilent, Santa Clara, CA, USA) was performed in all patients to identify size and location of chromosome 18 deletion. (nih.gov)
  • Patients with 18q deletions frequently suffer from autoimmune disorders, recurrent infections, and allergy due to immune dysregulation presenting with variable antibody deficiencies and T-regulatory cell deficiency (CD4+CD25+CD127lowFOXP3+). (nih.gov)
  • For those with secondary forms of GH resistance, other than that due to GH inactivating antibodies in rhGH-treated patients with GH1 gene deletion who require rhIGF-I treatment, the underlying cause (eg, malnutrition, liver disease) should be identified and treated appropriately. (medscape.com)
  • We enrolled 199 non-22q11.2 deletion patients with CTDs and 139 unrelated healthy controls. (biomedcentral.com)
  • This is the first human missense mutation showing that TBX1 is a candidate causing isolated CTDs in Chinese patients without 22q11.2 deletion. (biomedcentral.com)
  • To better address the issue of the link between TBX1 and isolated CTDs, we performed TBX1 gene sequencing in a large sample of Chinese isolated CTDs patients without 22q11.2 deletion. (biomedcentral.com)
  • Results: Chromosome 22q11.2 deletion was detected in 2 patients. (jcpres.com)
  • One of these patients had anal stenosis, minor cardiac abnormalities, and a small 0.89-Mb deletion. (jcpres.com)
  • The overlapping genes in the deletion regions of the 2 patients were the DGCR5, DGCR6, and PRODH genes. (jcpres.com)
  • [ 6 ] Wilms tumor occurs in more than 30% of patients with 11p13 deletions. (medscape.com)
  • Diagnosis requires cytogenetic analysis and molecular characterization and should include a search for a translocation because deletion may be the result of transmission of a derivative chromosome. (orpha.net)
  • Prenatal diagnosis is feasible and genetic counseling should be proposed and depends on the cytogenetic rearrangement responsible for the deletion ( de novo or translocation). (orpha.net)
  • 3 ] described another 28 individuals with pure terminal 6q deletions diagnosed by conventional cytogenetic methods or array CGH, with all findings confirmed by FISH. (biomedcentral.com)
  • Molecular genetic diagnosis can be performed using sequencing and deletion/duplication analysis of the genes NIPBL , SMC3 , RAD21 , SMC1A , and HDAC8 . (medscape.com)
  • Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. (aacrjournals.org)
  • Pure subtelomeric deletions involving 10p15-ter are very rare ( (orpha.net)
  • Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs. (nature.com)
  • The phenotypes were comparable up to a deletion size of 7.1 Mb, and most features could be attributed to the terminally located gene DLL1 . (biomedcentral.com)
  • Based on our findings, we provide recommendations for clinical follow-up and surveillance of individuals with terminal 6q deletions. (biomedcentral.com)
  • This fact is consistent with clinical manifestations due to haploinsufficiency (ie, half-normal levels) of the gene product. (medscape.com)
  • Using data from the 100,000 Genomes Project, four unrelated individuals with intellectual disability (ID) were identified, each harbouring de novo whole gene deletions of SRRM2. (ox.ac.uk)
  • In the present study, we identified a heterozygous 51 bp deletion (c.1699_1749del51) in ACO2 in a family with autosomal dominant inherited isolated optic atrophy. (huji.ac.il)
  • Here, we report our findings on 93 individuals with terminal 6q deletions and 11 individuals with interstitial 6q26q27 deletions, a cohort that includes 38 newly identified individuals. (biomedcentral.com)
  • A complementation assay using aco1-deficient yeast revealed a growth defect for the mutant ACO2 variant substantiating a pathogenic effect of the deletion. (huji.ac.il)
  • It has been hypothesized that the mutation found in these subjects resulted in a loss of gene function resulting in obesity due to haploinsufficiency of the MC4R gene. (psu.edu)
  • If hemizygosity of the MC4R gene results in haploinsufficiency-induced obesity, then individuals with deletions of 18q whose deletions include the MC4R gene should be obese in comparison with those individuals whose deletion does not include the gene. (psu.edu)
  • We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions. (dspace-express.com)
  • They include two different frameshifts, one inframe deletion and one missense mutation. (bmj.com)
  • Smaller deletions involving the region 10p14-pter have been described in (orpha.net)
  • Subject B has a smaller deletion that does not remove BDNF. (medscape.com)
  • These results reveal bottom-up neurobiological mechanisms through which peripheral hearing loss arising from the 22q11.2 deletion may promote the emergence of schizophrenia-relevant auditory brain and behavioral abnormalities, and also suggest a link between conductive hearing loss and reduced PV+ interneuron density in the auditory cortex. (biorxiv.org)
  • These results suggest mechanisms through which hearing loss associated with the 22q11.2 deletion may promote emergence of schizophrenia-relevant auditory brain and behavioral abnormalities and indicate that conductive hearing loss may influence PV+ interneuron density in the auditory cortex. (biorxiv.org)
  • The deletion may involve only the terminal 10p15 band, or extend towards the centromere to bands 10p14 or 10p13. (orpha.net)
  • Terminal 6q deletions are rare, and the number of well-defined published cases is limited. (biomedcentral.com)
  • To date, two large reviews on terminal 6q deletions have been published. (biomedcentral.com)
  • Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. (dspace-express.com)
  • Such imbalances stem from under- or over-expression of a subunit of a complex consequent to a deletion, duplication or regulatory mutation of an allele encoding the relevant protein. (biomedcentral.com)
  • To gain insight into the biochemical bases of the effects of stoichiometric imbalances, we explore the consequences of under- or over-expression of a subunit of a complex due, for instance, to a deletion, duplication or regulatory mutation of an allele encoding the relevant protein in a diploid organism. (biomedcentral.com)
  • The second patient had anal atresia, immune deficiency, inguinal hernia, and a 2.7-Mb cryptic deletion. (jcpres.com)
  • Subject A has a large deletion on chromosome 11 that removes one copy of the BDNF gene. (medscape.com)
  • The size of the deletion varies among affected individuals, with most affected people missing 2 million to 9 million DNA building blocks (also written as 2 Mb to 9 Mb). (medlineplus.gov)
  • Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. (researchgate.net)
  • 18q deletion was confirmed by means of array CGH analysis in 27 individuals, 15 (55.6%) females and 12 males, referred to the project by specialists in medical genetics, diabetology, or pediatric endocrinology between May 2015 and December 2019. (nih.gov)
  • Deletion of the PAX6 gene, which plays a role in myelinization of the cerebral hemispheres during CNS development, may also be responsible for the mental retardation seen in the WAGR association. (medscape.com)