scholarly journals Identification of the FirstDe Novo UBIAD1Gene Mutation Associated with Schnyder Corneal Dystrophy

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Benjamin R. Lin ◽  
Ricardo F. Frausto ◽  
Rosalind C. Vo ◽  
Stephan Y. Chiu ◽  
Judy L. Chen ◽  
...  
Keyword(s):  
Family History ◽  
Missense Mutation ◽  
Protein Function ◽  
De Novo ◽  
Family Members ◽  
Corneal Dystrophy ◽  
Slit Lamp ◽  
Slit Lamp Examination ◽  
The Family ◽  
Schnyder Corneal Dystrophy

Purpose.To report the identification of the firstde novo UBIAD1missense mutation in an individual with Schnyder corneal dystrophy (SCD).Methods.A slit lamp examination was performed on a 47-year-old woman without a family history of corneal disorders. The proband’s parents, two sisters, and son were also examined and genomic DNA from all six individuals was collected. The exons and exon-intron boundaries ofUBIAD1were screened using Sanger sequencing. Identified mutations were screened for in 200 control chromosomes.In silicoanalysis predicted the impact of identified mutations on protein function and structure.Results.Slit lamp examination of the proband revealed findings consistent with SCD. Corneas of the family members appeared unaffected. Screening ofUBIAD1in the proband identified a novel heterozygous c.308C>T mutation, predicted to encode the missense amino acid substitution p.(Thr103Ile). This mutation was not identified in any of the family members or in 200 control chromosomes and was predicted to be damaging to normal protein function and structure.Conclusions.We present a novel heterozygousde novomissense mutation inUBIAD1, p.(Thr103Ile), identified in a patient with classic clinical features of SCD. This highlights the value of genetic testing in clinical diagnostic settings, even in the absence of a positive family history.

scholarly journals Identification of a Novel Missense KRT12 Mutation in a Vietnamese Family with Meesmann Corneal Dystrophy

2020 ◽  
Vol 11 (1) ◽  
pp. 120-126
Author(s):  
Pham Ngoc Dong ◽  
Le Xuan Cung ◽  
Tran Khanh Sam ◽  
Do Thi Thuy Hang ◽  
Doug D. Chung ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Novel Mutation ◽  
Family Members ◽  
Corneal Dystrophy ◽  
Slit Lamp ◽  
Slit Lamp Examination ◽  
Corneal Epithelial ◽  
Epithelial Phenotype ◽  
History Of ◽  
Characteristic Features

Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.

A novel missense mutation of CRYBB1 causes congenital cataract in a Chinese family

2020 ◽  
pp. 112067212091449
Author(s):  
Yanan Ji ◽  
Xiangyu Zhao ◽  
Juanmei Zhang ◽  
Dan Zhang ◽  
Chunliu Tian ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Protein Function ◽  
Congenital Cataract ◽  
Family Members ◽  
Causative Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Nuclear Cataract ◽  
Mutation Site ◽  
The Family

Objective of the study: To identify the pathogenic gene and mutation site of a Chinese family with congenital cataract. Methods: Eight family members and 100 controls were employed, and targeted exome sequencing was used to identify the genetically pathogenic factor of the proband. Results: Targeted next-generation sequencing identified a novel missense mutation c.209A>C (p.Q70P) of CRYBB1 gene in the family. Sanger sequencing results showed that this heterozygous mutation was a causative mutation, which was not found in unaffected family members and healthy controls. Bioinformatics predicts that the effect of this mutation on protein function is probably harmful. Conclusion: We demonstrate that c.209A>C of CRYBB1 gene is a pathogenic mutation in the family of congenital nuclear cataract in this study. This is the first report that this mutation leads to congenital nuclear cataract, which broadens the mutation spectrum of CRYBB1 gene in congenital nuclear cataract.

scholarly journals Multimodal Imaging Features of Schnyder Corneal Dystrophy

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Wassim Ghazal ◽  
Cristina Georgeon ◽  
Kate Grieve ◽  
Nacim Bouheraoua ◽  
Vincent Borderie
Keyword(s):  
Optical Coherence Tomography ◽  
Cross Sections ◽  
Multimodal Imaging ◽  
Corneal Dystrophy ◽  
Slit Lamp ◽  
Slit Lamp Examination ◽  
En Face ◽  
Schnyder Corneal Dystrophy ◽  
Corneal Crystals

Objective. To describe the multimodal imaging of Schnyder corneal dystrophy. Methods. Seven eyes of seven patients (5 female and 2 male patients) aged 52 to 92 years were included in this prospective observational study. Diagnosis of SCD was confirmed by histology after keratoplasty. In vivo multimodal imaging consisted of spectral domain-optical coherence tomography with cross sections, en face scans, corneal pachymetry, and epithelial mapping, and in vivo confocal microscopy was recorded. Ex vivo full-field optical coherence tomography scans of two corneal buttons were analyzed. The seven corneal buttons obtained during penetrating or deep anterior lamellar keratoplasty were processed for light microscopy. Results. Slit-lamp examination showed central stromal opacities, arcus lipoides, and midperipheral haze. Corneal crystals were found in 2 out of 7 eyes. SD-OCT cross sections and en face scans showed diffuse hyperreflectivity of the anterior, mid, and posterior stroma with a maximum in the anterior stroma, hyporeflective stromal striae, and epithelial hyperreflectivity. Central corneal thickness ranged from 507 to 635 μm. IVCM revealed hyperreflective deposits in the epithelium and throughout the stroma, thin subepithelial nerves, and needle-shaped and rectangular crystals. Keratocyte nuclei were rare or undetectable. FF-OCT scans confirmed the presence of small round and needle-shaped hyperreflective deposits in the epithelium and stroma. Histology revealed vacuolization of the basal epithelial cells and empty interlamellar stromal vacuoles. Conclusion. High-resolution multimodal imaging demonstrates the characteristic features of SCD which involve both the corneal epithelium and stroma, and it provides diagnosis confirmation even in eyes with no visible corneal crystals at slit-lamp examination.

FAMILY TENSION AS A CAUSE OF COLIC IN INFANTS

PEDIATRICS ◽  
1956 ◽  
Vol 18 (5) ◽  
pp. 835-836
Author(s):  
John C. Cobb
Keyword(s):  
Family History ◽  
Allergic Disease ◽  
Family Members ◽  
Clinical Impression ◽  
Family Histories ◽  
The Family

A study of colic in infancy was undertaken as part of the Yale Rooming-In Project. The longitudinal records of 98 infants who were study subjects were analyzed with respect to incidence, duration, and severity of colic. Forty-eight of the infants were classified as fussy or colicky and 50 as contented. Because I had formed the clinical impression that allergy was an important contributing factor in the causation of colic, careful family histories were taken for all of these infants with particular attention to allergic disease in any member of either parent's family. An adequate family history was obtained in 95 of these infants. These data were analyzed both according to the incidence of allergic disease and according to the severity of allergic disease in family members. Among the relatives of the 45 "fussy" or "colicky" infants 7.3 per cent had severe allergy, 17.7 pen cent had mild allergy and 74 per cent had little or no allergy. Among the relatives of the 50 contented infants 7.6 per cent had severe allergy, 14.7 per cent had mild allergy and 77 per cent had no allergy. The family histories included a total of 957 relatives. The 45 families of the babies who were fussy or colicky were divided as follows as to amount of allergy among the relatives. In 7 families there was much allergy, in 30 families there was some allergy and in 8 families there was little or no allergy. The [See Table I in Source PDF] families of the 50 contented infants were divided as follows, in 7 families there was much allergy, in 33 there was some allergy and in 10 there was little on no allergy.

Congenital cholesteatoma in siblings

2013 ◽  
Vol 127 (11) ◽  
pp. 1143-1144 ◽  
Author(s):  
L D Landegger ◽  
M S Cohen
Keyword(s):  
Computed Tomography ◽  
Case Report ◽  
Family History ◽  
Physical Examination ◽  
Age At Onset ◽  
Family Members ◽  
Initial Presentation ◽  
Congenital Cholesteatoma ◽  
The Family ◽  
Hereditary Factors

AbstractIntroduction:The exact aetiology of congenital cholesteatoma, the less common form of this destructive disease, is still under debate.Case report:A two-year-old boy was referred to paediatric otolaryngology with persistent, bloody, left-sided otorrhoea refractory to oral and ototopical antibiotics. Prior to its onset at age 16 months, all ear examinations on the affected side were normal. Physical examination, imaging with computed tomography and eventual tympanomastoidectomy revealed extensive cholesteatoma. The extent of the disease, age at onset of symptoms and absence of otological disease before initial presentation suggested the diagnosis of congenital cholesteatoma. Review of the family history revealed that the patient's older brother had undergone tympanomastoidectomy for a small, well-encapsulated, mesotympanic congenital cholesteatoma at two years of age.Discussion:This case joins a single, previous report describing congenital cholesteatoma in multiple family members, suggesting that in some cases, hereditary factors may play a role in the formation of the disease.

scholarly journals A Missense Mutation in OPA1 Causes Dominant Optic Atrophy in a Chinese Family

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shaoyi Mei ◽  
Xiaosheng Huang ◽  
Lin Cheng ◽  
Shiming Peng ◽  
Tianhui Zhu ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Optic Atrophy ◽  
Clinical Characteristics ◽  
Hand Movement ◽  
Family Members ◽  
Clinical Manifestations ◽  
Chinese Family ◽  
Variable Degree ◽  
Dominant Optic Atrophy ◽  
The Family

Background. To investigate the genetic causes and clinical characteristics of dominant optic atrophy (DOA) in a Chinese family. Methods. A 5-generation pedigree of 35 family members including 12 individuals affected with DOA was recruited from Shenzhen Eye Hospital, China. Four affected family members and one unaffected family member were selected for whole exome sequencing. Sanger sequencing was used to confirm and screen the identified mutation in 18 members of the family. The disease-causing mutation was identified by bioinformatics analysis and confirmed by segregation analysis. The clinical characteristics of the family members were analyzed. Results. A heterozygous missense mutation (c.1313A>G, p.D438G) in optic atrophy 1 (OPA1) was identified in 10 individuals affected with DOA in this family. None of the unaffected family members had the mutation. Patients in this family had vision loss since they were children or adolescence. The visual acuity decreased progressively to hand movement, except for one patient (IV-12) who had relatively good vision of 20/30 and 20/28. The fundus typically manifested as optic disc pallor. The visual fields, optical coherence tomography, and visual evoked potential suggested variable degree of abnormality in patients. Patients who had a history of cigarette smoking and alcohol drinking had more severe clinical manifestations. Conclusions. Our results suggest that the p.D438G mutation in OPA1 causes optic atrophy in this family. The patients who carried the mutation demonstrated heterogeneous clinical manifestations in this family. This is the first report on the c.1313A>G (p.D438G) mutation of OPA1 in a Chinese family affected with DOA.

scholarly journals De novo arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia

2016 ◽  
Vol 17 (3) ◽  
pp. 330-335 ◽  
Author(s):  
Yusuke Shimoda ◽  
Toshiya Osanai ◽  
Naoki Nakayama ◽  
Satoshi Ushikoshi ◽  
Masaaki Hokari ◽  
...  
Keyword(s):  
Family History ◽  
Arteriovenous Malformation ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Autosomal Dominant ◽  
De Novo ◽  
The Family ◽  
Systemic Disorder ◽  
History Of ◽  
Cerebral Avms

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant systemic disorder characterized by the enlargement of capillaries, recurrent nosebleeds, and multiple arteriovenous malformations (AVMs). Although cerebral AVMs are traditionally considered to be congenital lesions, some reports have described de novo AVMs, which suggests that the authors believed them to be dynamic conditions. In this article, the authors describe the case of a 5-year-old boy with HHT in whom a de novo cerebral AVM was detected after a negative MRI result at 5 months. To the authors’ knowledge, this is the first report of a de novo AVM in a patient with HHT. In patients with a family history of HHT, de novo AVMs are possible, even when no lesions are detected at the first screening. Therefore, regular screenings need to be performed, and the family should be informed that AVMs could still develop despite normal MRI results.

Familial Gliomas

Neurosurgery ◽  
1982 ◽  
Vol 10 (4) ◽  
pp. 445-449 ◽  
Author(s):  
William M. Chadduck ◽  
Martin G. Netsky
Keyword(s):  
Family History ◽  
Chromosomal Abnormalities ◽  
Family Members ◽  
Careful Attention ◽  
Genetic Studies ◽  
The Family ◽  
Cerebral Gliomas ◽  
History Of

Abstract Four families having multiple family members with cerebral gliomas are presented. Genetic studies were done in some, but no chromosomal abnormalities were found in this group of patients or their families. The authors recommend that careful attention be given to the family history of all glioma patients and that more extensive genetic studies be done. The formation of a registry to report cases of familial gliomas is also suggested.

Family History of Children with Developmental Language Disorders

1986 ◽  
Vol 63 (2) ◽  
pp. 655-658 ◽  
Author(s):  
Jean Neils ◽  
Dorothy M. Aram
Keyword(s):  
Family History ◽  
Family Members ◽  
Language Disorders ◽  
Normal Control Group ◽  
Control Group ◽  
Reported Speech ◽  
Normal Children ◽  
Developmental Language Disorders ◽  
The Family ◽  
History Of

The present study shows the increased incidence of language-related disorders among family members of children with language disorders. The family histories of 74 children with developmental language disorders and 36 normal children were compared. The children with language disorders had significantly more family members who reported speech, stuttering, reading, and language disorders than the normal control group.

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.

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