scholarly journals A New Case of 13q12.2q13.1 Microdeletion Syndrome Contributes to Phenotype Delineation

2014 ◽  
Vol 2014 ◽  
pp. 1-5
Author(s):  
Giorgia Mandrile ◽  
Eleonora Di Gregorio ◽  
Alessandro Calcia ◽  
Alessandro Brussino ◽  
Enrico Grosso ◽  
...  
Keyword(s):  
Clinical Features ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Genetic Disorder ◽  
Phenotypic Expression ◽  
Microdeletion Syndrome ◽  
Complex Rearrangement

A recently described genetic disorder has been associated with 13q12.3 microdeletion spanning three genes, namely,KATNAL1, LINC00426, andHMGB1. Here, we report a new case with similar clinical features that we have followed from birth to 5 years old. The child carried a complex rearrangement with a double translocation: 46,XX,t(7;13)(p15;q14),t(11;15)(q23;q22). Array-CGH identified ade novomicrodeletion at 13q12.2q13.1 spanning 3–3.4 Mb and overlapping 13q12.3 critical region. Clinical features resembling those reported in the literature confirm the existence of a distinct 13q12.3 microdeletion syndrome and provide further evidence that is useful to characterize its phenotypic expression during the 5 years of development.

scholarly journals A de novo 2.78-Mb duplication on chromosome 21q22.11 implicates candidate genes in the partial trisomy 21 phenotype

2016 ◽  
Vol 1 (1) ◽  
Author(s):  
James D Weisfeld-Adams ◽  
Amanda K Tkachuk ◽  
Kenneth N Maclean ◽  
Naomi L Meeks ◽  
Stuart A Scott
Keyword(s):  
Candidate Genes ◽  
Clinical Features ◽  
Critical Region ◽  
Trisomy 21 ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Partial Trisomy ◽  
Chromosome 21 ◽  
Comparative Genomic Hybridisation ◽  
Comparative Genomic

Abstract Down syndrome (DS) is the most common genetic cause of intellectual disability (ID) and in the majority of cases is the result of complete trisomy 21. The hypothesis that the characteristic DS clinical features are due to a single DS critical region (DSCR) at distal chromosome 21q has been refuted by recently reported segmental trisomy 21 cases characterised by microarray-based comparative genomic hybridisation (aCGH). These rare cases have implicated multiple regions on chromosome 21 in the aetiology of distinct features of DS; however, the map of chromosome 21 copy-number aberrations and their associated phenotypes remains incompletely defined. We report a child with ID who was deemed very high risk for DS on antenatal screening (1 in 13) and has partial, but distinct, dysmorphologic features of DS without congenital heart disease (CHD). Oligonucleotide aCGH testing of the proband detected a previously unreported de novo 2.78-Mb duplication on chromosome 21q22.11 that includes 16 genes; however, this aberration does not harbour any of the historical DSCR genes (APP, DSCR1, DYRK1A and DSCAM). This informative case implicates previously under-recognised candidate genes (SOD1, SYNJ1 and ITSN1) in the pathogenesis of specific DS clinical features and supports a critical region for CHD located more distal on chromosome 21q. In addition, this unique case illustrates how the increasing resolution of microarray and high-throughput sequencing technologies can continue to reveal new biology and enhance understanding of widely studied genetic diseases that were originally described over 50 years ago.

A de novo deletion in a boy with cerebral palsy suggests a refined critical region for the 4q21.22 microdeletion syndrome

2017 ◽  
Vol 173 (5) ◽  
pp. 1287-1293 ◽  
Author(s):  
Mehdi Zarrei ◽  
Daniele Merico ◽  
Barbara Kellam ◽  
Worrawat Engchuan ◽  
Tara Scriver ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Critical Region ◽  
De Novo ◽  
Microdeletion Syndrome

Three-Year Follow-Up of a Prenatally Ascertained Apparently Non-Mosaic sSMC(10): Delineation of a Non-Critical Region

2015 ◽  
Vol 147 (4) ◽  
pp. 209-211
Author(s):  
Laura Barranco ◽  
Marta Costa ◽  
Elisabet Lloveras ◽  
Elena Ordóñez ◽  
Nerea Maiz ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Pericentromeric Region ◽  
Normal Female ◽  
Chromosome 10 ◽  
Mosaic Form ◽  
Small Supernumerary Marker Chromosomes

Small supernumerary marker chromosomes (sSMC) originating from chromosome 10 are rare and usually found in mosaic form. We present a de novo apparently non-mosaic sSMC(10) prenatally diagnosed in amniotic fluid and postnatally confirmed in peripheral blood. Characterization by array-CGH showed a pericentromeric duplication of 7.1 Mb of chromosome 10. The fetus did not show ultrasound abnormalities, and a normal female phenotype was observed during a 3-year postnatal follow-up. The absence of phenotypic abnormalities in the present case provides evidence of a non-critical pericentromeric region in 10p11.21q11.1 (hg19 35,355,570-42,448,569) associated with a duplication.

scholarly journals Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan Li ◽  
Ke-wang Xi ◽  
Ting Liu ◽  
Ying Zhang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Germline Mosaicism ◽  
Third Generation Sequencing ◽  
Neurological Features ◽  
Hands And Feet ◽  
Abnormal Behaviors

Abstract Background Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

scholarly journals Prenatal Diagnosis of 4p and 4q Subtelomeric Microdeletion in De Novo Ring Chromosome 4

2013 ◽  
Vol 2013 ◽  
pp. 1-5
Author(s):  
Halit Akbas ◽  
Naci Cine ◽  
Mahmut Erdemoglu ◽  
Ahmet Engin Atay ◽  
Selda Simsek ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Critical Region ◽  
Array Cgh ◽  
De Novo ◽  
Ring Chromosome ◽  
Maternal Serum ◽  
Chromosome 4 ◽  
Maternal Serum Screening ◽  
Ring Chromosomes ◽  
Subtelomeric Deletion

Ring chromosomes are unusual abnormalities that are observed in prenatal diagnosis. A 23-year-old patient (gravida 1, para 0) referred for amniocentesis due to abnormal maternal serum screening result in the 16th week of second pregnancy. Cytogenetic analysis of cultured amniyotic fluid cells revealed out ring chromosome 4. Both maternal and paternal karyotypes were normal. Terminal deletion was observed in both 4p and 4q arms of ring chromosome 4 by fluorescence in situ hybridization (FISH). However deletion was not observed in the WHS critical region of both normal and ring chromosome 4 by an additional FISH study. These results were confirmed by means of array-CGH showing terminal deletions on 4p16.3 (130 kb) and 4q35.2 (2.449 Mb). In the 21th week of pregnancy, no gross anomalia, except two weeks symmetric growth retardation, was present in the fetal ultrasonographic examination. According to our review of literature, this is the first prenatal case with 4p and 4q subtelomeric deletion of ring chromosome 4 without the involvement of WHS critical region. Our report describes the prenatal case with a ring chromosome 4 abnormality completely characterized by array-CGH which provided complementary data for genetic counseling of prenatal diagnosis.

Characterization of the Phenotype Associated with Microduplication Reciprocal to NF1 Microdeletion Syndrome

2017 ◽  
Vol 152 (1) ◽  
pp. 22-28
Author(s):  
Elisa Tassano ◽  
Thea Giacomini ◽  
Mariasavina Severino ◽  
Alessandra Gamucci ◽  
Patrizia Fiorio ◽  
...  
Keyword(s):  
Clinical Features ◽  
Array Cgh ◽  
Clinical Phenotype ◽  
Rare Condition ◽  
Genetic Data ◽  
Neurofibromatosis Type ◽  
Microdeletion Syndrome

17q11.2 microduplication syndrome is a recently described relatively rare condition associated with a nonspecific phenotype. Intellectual disability, developmental delay, and dysmorphisms are the only clinical features common to a majority of cases. Seventeen patients have been reported so far. Here, we present another patient with 17q11.2 duplication and no signs of neurofibromatosis type 1, identified by array-CGH. We compared clinical features and genetic data with those of previously reported patients with 17q11.2 microduplications. We also analyzed the gene content of the duplicated region in order to investigate the possible role of specific genes in the clinical phenotype of our patient.

scholarly journals De Novo Loss-of-Function Mutations in SETD5, Encoding a Methyltransferase in a 3p25 Microdeletion Syndrome Critical Region, Cause Intellectual Disability

2014 ◽  
Vol 94 (4) ◽  
pp. 618-624 ◽  
Author(s):  
Detelina Grozeva ◽  
Keren Carss ◽  
Olivera Spasic-Boskovic ◽  
Michael J. Parker ◽  
Hayley Archer ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Critical Region ◽  
De Novo ◽  
Loss Of Function ◽  
Microdeletion Syndrome

scholarly journals Expanding the Clinical Spectrum of Sotos Syndrome in a Patient with the New “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]” NSD1 Missense Mutation and Complex Skin Hamartoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3189
Author(s):  
Annalisa Mencarelli ◽  
Paolo Prontera ◽  
Amedea Mencarelli ◽  
Daniela Rogaia ◽  
Gabriela Stangoni ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Control Cell ◽  
Functional Domain ◽  
Sotos Syndrome ◽  
Organ Systems ◽  
Increased Risk ◽  
The Right

Sotos syndrome is one of the most common overgrowth diseases and it predisposes patients to cancer, generally in childhood. The prevalence of this genetic disorder is 1:10,000–1:50,000, and it is characterized by wide allelic heterogeneity, with more than 100 different known mutations in the nuclear receptor-binding SET domain containing protein 1 (NSD1) gene. Most of these alterations are deletions and common micro-deletions with haploinsufficiency. Singular variants are missense mutations. The present study reports a case of a 4-year-old boy with specific clinical features of Sotos syndrome and a particular complex skin hamartoma on the right femoral side, in addition to other minor findings, such as a “café-au-lait” spot on the right hemithorax and syndactyly of the second and third right toes. NSD1 gene analysis identified a de novo missense mutation, “c.[5867T>A]+[=]”; “p.[Leu1956Gln]+[=]”, that was not previously described in the literature. This mutation was localized to the functional domain of the gene and was likely the cause of Sotos syndrome in our patient. We also compared aspects of our patient’s condition with the clinical features of tuberous sclerosis (TSC), which is an autosomal neurocutaneous syndrome caused by mutations in the TSC1/TSC2 genes. These genes control cell growth and cell survival. This disorder is characterized by hamartomas in multiple organ systems, several coetaneous abnormalities, epilepsy, and increased risk of several types of tumors.

scholarly journals Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
The Central Nervous System ◽  
Null Mutant Mice

AbstractThe 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

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