scholarly journals Atypical Deletion of Williams-beuren Syndrome Reveals the Mechanism of Neurodevelopmental Disorders

2021 ◽  
Author(s):  
Jianrong Zhou ◽  
Ying Zheng ◽  
Guiying Liang ◽  
Xianyu Qin ◽  
Hang Yang ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Gene Deletion ◽  
Chromosomal Region ◽  
Clinical Phenotype ◽  
Growth Restriction ◽  
Physical Growth ◽  
Hemizygous Deletion ◽  
Neurodevelopmental Abnormalities ◽  
Craniofacial Features ◽  
Chromosome Microarray

Abstract Background The Williams-Beuren syndrome (WBS) is a multiple phylogenetic disorder, caused by the hemizygous deletion of 1.55 to 1.84 Mb on chromosome 7q11.23, which encodes a fragment of 26 to 28 genes. Among these genes, the deletion of the elastin (ELN) gene haplotype is the main cause of cardiovascular abnormalities. Other genes, such as CLIP2, GTF2IRD1, and GTF2I, may be associated with specific cognitive and craniofacial features. However, genes associated with specific neurocognitive phenotypes are still controversially discussed. The purpose of this study is to further explore the mechanism of neurodevelopmental disorders in patients with Williams-Beuren syndrome.Patients and methods Patients who had been diagnosed with WBS were recruited. The deletion was precisely defined by chromosome microarray analysis and the clinical phenotype was evaluated. Results This study identified nine patients with atypical deletions from 111 patients with WBS. One patient had normal neurodevelopmental with deletion of Williams-Beuren syndrome chromosomal region (WBSCR) telomere side genes, including GTF2I and GTF2IRD1, while another patient retained these genes but showed neurodevelopmental abnormalities. Seven of the eight patients with the WBSCR22 gene deletion developed growth restriction.Conclusions By comparing the genotype and phenotype of patients with typical deletions and atypical deletions, the deletion of GTF2I and GTF2IRD1 genes alone insufficient to induce typical neurocognitive phenotypes in WBS patients. The BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS. Furthermore, the deletion of the WBSCR22 gene may be the main cause of physical growth restriction in WBS patients.

scholarly journals Atypical Deletion of Williams-Beuren Syndrome Reveals the Mechanism of Neurodevelopmental Disorders

2020 ◽  
Author(s):  
Jianrong Zhou ◽  
Ying Zheng ◽  
Guiying Liang ◽  
Xianyu Qin ◽  
Hang Yang ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Gene Deletion ◽  
Chromosomal Region ◽  
Clinical Phenotype ◽  
Growth Restriction ◽  
Physical Growth ◽  
Hemizygous Deletion ◽  
Neurodevelopmental Abnormalities ◽  
Craniofacial Features ◽  
Chromosome Microarray

Abstract Background The Williams-Beuren syndrome (WBS) is a multiple phylogenetic disorder, caused by the hemizygous deletion of 1.55 to 1.84 Mb on chromosome 7q11.23, which encodes a fragment of 26 to 28 genes. Among these genes, the deletion of the elastin (ELN) gene haplotype is the main cause of cardiovascular abnormalities. Other genes, such as CLIP2, GTF2IRD1, and GTF2I, may be associated with specific cognitive and craniofacial features. However, genes associated with specific neurocognitive phenotypes are still controversially discussed. The purpose of this study is to further explore the mechanism of neurodevelopmental disorders in patients with Williams-Beuren syndrome.Patients and methods Patients who had been diagnosed with WBS were recruited. The deletion was precisely defined by chromosome microarray analysis and the clinical phenotype was evaluated. Results This study identified nine patients with atypical deletions from 111 patients with WBS. One patient had normal neurodevelopmental with deletion of Williams-Beuren syndrome chromosomal region (WBSCR) telomere side genes, including GTF2I and GTF2IRD1, while another patient retained these genes but showed neurodevelopmental abnormalities. Seven of the eight patients with the WBSCR22 gene deletion developed growth restriction.Conclusions By comparing the genotype and phenotype of patients with typical deletions and atypical deletions, the deletion of GTF2I and GTF2IRD1 genes alone insufficient to induce typical neurocognitive phenotypes in WBS patients. The BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS. Furthermore, the deletion of the WBSCR22 gene may be the main cause of physical growth restriction in WBS patients.

scholarly journals Rare Pathogenic Copy Number Variation in the 16p11.2 (BP4–BP5) Region Associated with Neurodevelopmental and Neuropsychiatric Disorders: A Review of the Literature

2020 ◽  
Vol 17 (24) ◽  
pp. 9253
Author(s):  
Natália Oliva-Teles ◽  
Maria Chiara de Stefano ◽  
Louise Gallagher ◽  
Severin Rakic ◽  
Paula Jorge ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Copy Number ◽  
Chromosomal Region ◽  
Current Knowledge ◽  
Copy Number Variants ◽  
Inclusion Criteria ◽  
Rare Disorders ◽  
Number Variation ◽  
Malformation Syndromes ◽  
Neuropsychiatric Conditions

Copy number variants (CNVs) play an important role in the genetic underpinnings of neuropsychiatric/neurodevelopmental disorders. The chromosomal region 16p11.2 (BP4–BP5) harbours both deletions and duplications that are associated in carriers with neurodevelopmental and neuropsychiatric conditions as well as several rare disorders including congenital malformation syndromes. The aim of this article is to provide a review of the current knowledge of the diverse neurodevelopmental disorders (NDD) associated with 16p11.2 deletions and duplications reported in published cohorts. A literature review was conducted using the PubMed/MEDLINE electronic database limited to papers published in English between 1 January 2010 and 31 July 2020, describing 16p11.2 deletions and duplications carriers’ cohorts. Twelve articles meeting inclusion criteria were reviewed from the 75 articles identified by the search. Of these twelve papers, eight described both deletions and duplications, three described deletions only and one described duplications only. This study highlights the heterogeneity of NDD descriptions of the selected cohorts and inconsistencies concerning accuracy of data reporting.

Deletion of chromosomal region Xq28 cause of Hunter syndrome in a patient with mild clinical phenotype

2019 ◽  
Vol 126 (2) ◽  
pp. S156
Author(s):  
Natalia V. Zhurkova ◽  
Kirill Victorovich Savostyanov ◽  
Alexandr Andreevich Pushkov ◽  
Tatiana Vladimirovna Podkletnova ◽  
Nato Dzhumberovna Vashakmadze ◽  
...  
Keyword(s):  
Chromosomal Region ◽  
Clinical Phenotype ◽  
Hunter Syndrome ◽  
Mild Clinical Phenotype

scholarly journals The First Description of Monozygotic Twin Females Discordant for the Craniofrontonasal Syndrome Phenotype and the Report of Four Novel Pathogenic Variants in the EFNB1 Gene

2021 ◽  
Author(s):  
Ewelina Bukowska-Olech ◽  
Paweł Gawliński ◽  
Anna Jakubiuk-Tomaszuk ◽  
Maria Jędrzejowska ◽  
Ewa Obersztyn ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Clinical Phenotype ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Pathogenic Variants ◽  
Phenotypic Spectrum ◽  
Targeted Ngs ◽  
Primary Finding ◽  
Unusual Phenomenon ◽  
Craniofacial Features

Abstract Background: Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that results from pathogenic variants in the EFNB1 gene. The syndrome paradoxically presents with greater severity of the symptoms in heterozygous females than hemizygous males.Results: Our primary finding was the description of monozygotic twins, i.e., patients 5 & 6, discordant for the CFNS phenotype. Intriguingly, patient 5 presented classical CFNS gestalt, whereas patient 6 manifested only very subtle craniofacial features, not resembling CFNS. Besides, we have expanded the mutational spectrum of the EFNB1 gene through reporting four novel pathogenic variants – p.(Trp12*), p.(Cys64Phe), p.(Tyr73Metfs*86), p.(Glu210*). All those alterations were found applying either targeted NGS of a custom gene panel or PCR followed by Sanger sequencing and evaluated using in silico predictors. Lastly, we have also expanded the CFNS phenotypic spectrum by describing in patient 3 novel features of the syndrome, such as bifid hallux, bicornuate uterus, and abnormal right ovary segmented into six parts Conclusions: We have described the unreported so far differences of the clinical phenotype in the monozygotic twin patients 5 & 6 harbouring an identical p.(Glu210*) variant located in the EFNB1 gene. With our finding, we have pointed to an unusual phenomenon of mildly affected females with CFNS, who may not manifest features suggestive of the syndrome. Consequently, this study may be valuable for geneticists consulting patients with craniofacial disorders.

A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys

2018 ◽  
Vol 94 (3-4) ◽  
pp. 303-312
Author(s):  
Y.A. Ito ◽  
A.C. Smith ◽  
K.D. Kernohan ◽  
I.A. Pena ◽  
A. Ahmed ◽  
...  
Keyword(s):  
Growth Restriction ◽  
Craniofacial Features

scholarly journals Neurodevelopmental Impairment As the Main Phenotypic Hallmark Associated with the Translocation t(7;10)(7p22.3;q26.11)

2020 ◽  
Author(s):  
Mario Mastrangelo ◽  
Barbara Torres ◽  
Gloria De Vita ◽  
Marina Goldoni ◽  
Agnese De Giorgi ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Clinical Phenotype ◽  
Muscle Tone ◽  
Gene Dosage ◽  
Dosage Effect ◽  
Pathogenic Role ◽  
Gene Dosage Effect ◽  
Severe Intellectual Disability ◽  
Neurodevelopmental Impairment ◽  
Neurodevelopmental Abnormalities

AbstractReported here is a novel patient carrying an unbalanced t (10q26.11-q26.3; 7p22.3) and presenting with a severe intellectual disability with autistic features, abnormalities of muscle tone, and a drug-responsive epilepsy. The prominence of neurological and neurodevelopmental abnormalities in the clinical phenotype highlights a possible pathogenic role for different genes in the involved regions. Hypothetical mechanisms may include a possible gene dosage effect for DOCK1 and/or haploinsufficiency of PRKAR1B SUN1, ADAP1, and GPER1.

scholarly journals Exome-First Approach in Fetal Akinesia Reveals Chromosome 1p36 Deletion Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-5
Author(s):  
Masatake Toshimitsu ◽  
Shinichi Nagaoka ◽  
Shuusaku Kobori ◽  
Maki Ogawa ◽  
Fumihiko Suzuki ◽  
...  
Keyword(s):  
Chromosomal Region ◽  
Deletion Syndrome ◽  
Chromosomal Microarray ◽  
Molecular Cytogenetic ◽  
Whole Exome ◽  
Fetal Movements ◽  
Cytogenetic Analyses ◽  
Craniofacial Features ◽  
Multiple Abnormalities ◽  
Chromosome 1P36

Background. Fetal akinesia refers to a broad spectrum of disorders with reduced or absent fetal movements. There is no established approach for prenatal diagnosis of the cause of fetal akinesia. Chromosome 1p36 deletion syndrome is the most common subtelomeric terminal deletion syndrome, recognized postnatally from typical craniofacial features. However, the influence of chromosome 1p36 deletion on fetal movements remains unknown. Case Report. A 32-week-old fetus with akinesia showed multiple abnormalities, including fetal growth restriction, congenital cardiac defects, and ventriculomegaly. G-banding analysis using cultured amniocytes revealed 46,XY,22pstk+. Postnatal whole exome sequencing and subsequent chromosomal microarray identified a 3 Mb deletion of chromosomal region 1p36.33–p36.32. These results of molecular cytogenetic analyses were consistent with the fetal sonographic findings. Conclusion. Using the exome-first approach, we identified a case with fetal akinesia associated with chromosome 1p36 deletion. Chromosome 1p36 deletion syndrome may be considered for differential diagnosis in cases of fetal akinesia with multiple abnormalities.

scholarly journals Clinical and molecular characterization of craniofrontonasal syndrome: new symptoms and novel pathogenic variants in the EFNB1 gene

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ewelina Bukowska-Olech ◽  
Paweł Gawliński ◽  
Anna Jakubiuk-Tomaszuk ◽  
Maria Jędrzejowska ◽  
Ewa Obersztyn ◽  
...  
Keyword(s):  
Clinical Phenotype ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Pathogenic Variants ◽  
Phenotypic Spectrum ◽  
Targeted Ngs ◽  
Primary Finding ◽  
Unusual Phenomenon ◽  
Craniofacial Features

Abstract Background Craniofrontonasal syndrome (CFNS) is a rare X-linked disorder that results from pathogenic variants in the EFNB1 gene. The syndrome paradoxically presents with greater severity of the symptoms in heterozygous females than hemizygous males. Results We have recruited and screened a female cohort affected with CFNS. Our primary finding was the description of monozygotic twins, i.e., patients 5 and 6, discordant for the CFNS phenotype. Intriguingly, patient 5 presented classical CFNS gestalt, whereas patient 6 manifested only very subtle craniofacial features, not resembling CFNS. Besides, we have expanded the mutational spectrum of the EFNB1 gene through reporting four novel pathogenic variants—p.(Trp12*), p.(Cys64Phe), p.(Tyr73Metfs*86), p.(Glu210*). All those alterations were found applying either targeted NGS of a custom gene panel or PCR followed by Sanger sequencing and evaluated using in silico predictors. Lastly, we have also expanded the CFNS phenotypic spectrum by describing in patient 3 several novel features of the syndrome, such as bifid hallux, bicornuate uterus, and abnormal right ovary segmented into six parts. Conclusions We have described the unreported so far differences of the clinical phenotype in the monozygotic twin patients 5 and 6 harboring an identical p.(Glu210*) variant located in the EFNB1 gene. With our finding, we have pointed to an unusual phenomenon of mildly affected females with CFNS, who may not manifest features suggestive of the syndrome. Consequently, this study may be valuable for geneticists consulting patients with craniofacial disorders.

scholarly journals A rare case of combined immunodeficiency due to a deletion of 11(q) – Jacobsen syndrome

2020 ◽  
Vol 19 (3) ◽  
pp. 114-120
Author(s):  
N. B. Kuzmenko ◽  
O. A. Shvets ◽  
A. A. Mukhina
Keyword(s):  
Clinical Phenotype ◽  
Psychomotor Retardation ◽  
Physical Growth ◽  
Facial Dysmorphism ◽  
Combined Immunodeficiency ◽  
Chromosome 11 ◽  
Partial Deletion ◽  
Nasal Bridge ◽  
Jacobsen Syndrome ◽  
Broad Nasal Bridge

Jacobsen syndrome (JS) is a rare combined immunodeficiency caused by partial deletion of the long arm of chromosome 11. Clinical features include physical growth retardation, psychomotor retardation, characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small low set ears). Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Abnormal platelet function and immunological problems are usually present. Here we describe a patient with deletion of 11(q) chromosome resulting in clinical phenotype of the facial dysmorphisms, congenital malformations, neurological symptoms, as well as clinical and laboratory features of immunodeficiency. Features of immune dysregulation in a patient with JS are clearly characterized. Patient's parents agreed to use personal dats and photos in research and publications.

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