A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of PITX2 and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay

2017 ◽  
Vol 151 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Živilė Maldžienė ◽  
Eglė Preikšaitienė ◽  
Salomėja Ignotienė ◽  
Natalija Kapitanova ◽  
Algirdas Utkus ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Pericentric Inversion ◽  
Patient Management ◽  
De Novo ◽  
Chromosomal Rearrangements ◽  
Genetic Alterations ◽  
Chromosome 4 ◽  
Rieger Syndrome ◽  
Craniofacial Dysmorphism ◽  
The Family

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of autosomal dominantly inherited malformations that predominantly affect the eye but are also associated with craniofacial dysmorphism and dental abnormalities. A broad spectrum of genetic alterations involving PITX2 and FOXC1 lead to ARS. We report on a 4-year-old girl with clinical features of ARS and developmental delay due to a de novo apparently balanced pericentric inversion in chromosome 4. This report emphasizes that complementary investigations are necessary to precisely characterize chromosomal rearrangements. Elucidation of the exact genetic cause of ARS is important for comprehensive genetic counseling of the family members and for better patient management.

Yq Microdeletion in a Patient with VACTERL Association and Shawl Scrotum with Bifid Scrotum: A Real Pathogenetic Association or a Coincidence?

2019 ◽  
Vol 158 (3) ◽  
pp. 121-125
Author(s):  
Stefano Tumini ◽  
Melissa Alfonsi ◽  
Silvia Carinci ◽  
Elisena Morizio ◽  
Ivana Antonucci ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Gene Mutations ◽  
Renal Dysplasia ◽  
Genetic Alterations ◽  
Vacterl Association ◽  
Severe Oligozoospermia ◽  
Azfc Region ◽  
Shh Pathway ◽  
Vertebral Defects

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.

scholarly journals New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Pten Mutation ◽  
Whole Exome ◽  
The Family ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background: Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. Methods: A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Results: Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. Conclusions: A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

Clinical and Cytogenomic Characterization of De Novo 11p14.3-p15.5 Duplication Associated with 18q23 Deletion in an Egyptian Female Infant

2020 ◽  
Author(s):  
Hanan H. Afifi ◽  
Ghada Y. El-Kamah ◽  
Alaa K. Kamel ◽  
Sally G. Abd Allah ◽  
Sayda Hammad ◽  
...  
Keyword(s):  
Developmental Delay ◽  
De Novo ◽  
Ductus Arteriosus ◽  
Chromosomal Rearrangements ◽  
Clinical Manifestations ◽  
Brain Magnetic Resonance Imaging ◽  
Comparative Genomic ◽  
Septal Hypertrophy

AbstractPaternal microduplication of 11p14.3-p15.5 causes the clinical manifestations of Beckwith–Wiedemann syndrome (BWS), while microdeletion of 18q23-ter is clinically characterized by short stature, congenital malformations, and developmental delay. We describe a 15-month-old girl presenting with protruding tongue, dysmorphic facial features, moderate developmental delay, umbilical hernia, hypotonia, mild-to-moderate pulmonary hypertension, small patent ductus arteriosus, and mild ventricular septal hypertrophy. Brain magnetic resonance imaging showed mild atrophic changes. Chromosomal analysis revealed 46, XX, add(18)(q23). Fluorescence in situ hybridization using subtelomere 18q and whole chromosome painting 18 showed subtelomere deletion in 18q, and the add segment was not derived from chromosome 18. Microarray-based comparative genomic hybridization detected a 22 Mb duplication of chromosome 11p15.5p14.3 and a 3.7 Mb deletion of chromosome 18q23. The phenotype of the chromosomal rearrangements is probably resulted from a combination of dosage-sensitive genes. Our patient had clinical manifestations of both 18q deletion and BWS.

scholarly journals Child with Deletion 9p Syndrome Presenting with Craniofacial Dysmorphism, Developmental Delay, and Multiple Congenital Malformations

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Nirmala D. Sirisena ◽  
U. Kalpani S. Wijetunge ◽  
Ramya de Silva ◽  
Vajira H. W. Dissanayake
Keyword(s):  
Developmental Delay ◽  
Congenital Malformations ◽  
Pulmonary Hypoplasia ◽  
De Novo ◽  
Left Lung ◽  
Chromosome 9 ◽  
Terminal Deletion ◽  
Sri Lankan ◽  
Craniofacial Dysmorphism ◽  
Complete Collapse

A 4-month-old Sri Lankan male child case with ade novoterminal deletion in the p22→pter region of chromosome 9 is described. The child presented with craniofacial dysmorphism, developmental delay, and congenital malformations in agreement with the consensus phenotype. A distinctive feature observed in this child was complete collapse of the left lung due to malformation of lung tissue. Cytogenetic studies confirmed terminal deletion of the short arm of chromosome 9 distal to band p22 [46,XY,del(9)(p22→pter)]. This is the first reported case of ade novodeletion 9p syndrome associated with pulmonary hypoplasia. This finding contributes to the widening of the spectrum of phenotypic features associated with deletion 9p syndrome.

De novo pericentric inversion of chromosome 4, inv(4)(p16q12) in a boy with piebaldism and mental retardation

2002 ◽  
Vol 113 (2) ◽  
pp. 190-192 ◽  
Author(s):  
A. Radha Ramadevi ◽  
Usha Naik ◽  
Usha Dutta ◽  
Srikanth ◽  
K. Prabhakara
Keyword(s):  
Mental Retardation ◽  
Pericentric Inversion ◽  
De Novo ◽  
Chromosome 4

scholarly journals New PTEN mutation identified in a patient with rare bilateral choroidal ganglioneuroma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhaoxin Jiang ◽  
Ting Zhang ◽  
Chonglin Chen ◽  
Limei Sun ◽  
Songshan Li ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Frameshift Mutation ◽  
De Novo ◽  
Family Members ◽  
Genetic Alterations ◽  
Unrelated Control ◽  
Whole Exome ◽  
The Family ◽  
Multiple Abnormalities ◽  
Human Genome Reference

Abstract Background Choroidal ganglioneuroma is an extremely rare tumor, and there is little knowledge regarding its pathogenesis. We aimed to investigate the phenotypic and genetic alterations in one sporadic patient with a rare case of bilateral choroidal ganglioneuroma. Methods A 6-year-old boy with histological diagnosis of bilateral ganglioneuroma was recruited for the study. Comprehensive ophthalmic examinations were performed. Genomic DNA was extracted from the peripheral blood samples collected from the patient, his unaffected family members, and 200 unrelated control subjects from the same population. Whole exome sequencing was performed and raw reads were aligned to the human genome reference (hg19) using Burrows-Wheeler Aligner. DNA from all available family members was Sanger sequenced for segregation analysis. Results Extensive bilateral retinal detachments were observed via optical coherence tomography. Diffuse thickening of choroid was identified with ultrasound B scan and magnetic resonance imaging. Genetic analysis revealed the presence of a novel heterozygous PTEN frameshift mutation, c.498delA (p.Thr167LeufsTer16), in exon 6. It was present in the affected individual, but not in any of the family members. Genetic analysis revealed that there was no mutation in neurofibromatosis-related genes in the family. Upon performing comprehensive systemic examinations, no obvious abnormalities in other organs were observed. Conclusions A novel de novo PTEN mutation was identified in a patient with bilateral choroidal ganglioneuroma. Although PTEN mutations are known to induce multiple abnormalities, choroidal ganglioneuroma can be the first manifestation without abnormalities in other organs. Further studies are needed to confirm the association between choroidal ganglioneuroma and PTEN mutation.

A Novel Variant in FOXC1 Associated With Atypical Axenfeld-Rieger Syndrome

2021 ◽  
Author(s):  
Rui Wang ◽  
Wei-Qian Wang ◽  
Xiao-Qin Li ◽  
Juan Zhao ◽  
Kun Yang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
De Novo ◽  
Late Onset ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Pathogenic Variant ◽  
Rieger Syndrome ◽  
Craniofacial Dysmorphism ◽  
Whole Exome ◽  
Novel Variant

Abstract Background Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, therefore, clinical diagnosis present a huge challenge. Results In this study, we described a pathogenic variant in FOXC1 in one 5 year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linked to the FOXC1 variant and is coincidental. Conclusions Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.

scholarly journals A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rui Wang ◽  
Wei-Qian Wang ◽  
Xiao-Qin Li ◽  
Juan Zhao ◽  
Kun Yang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
De Novo ◽  
Late Onset ◽  
Genetic Disorder ◽  
Genetic Diagnosis ◽  
Rieger Syndrome ◽  
Craniofacial Dysmorphism ◽  
Whole Exome ◽  
Ocular Disorders ◽  
Novel Variant

AbstractMutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling.

Sign in / Sign up

Export Citation Format

Share Document