Novel Frizzled-4 Gene Mutations in Chinese Patients With Familial Exudative Vitreoretinopathy

Abstract Purpose This study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features. Methods Thirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments. Results Four novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5’UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100). Conclusions Our results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

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Rare and novel GNAS gene mutations in Chinese patients with thyroid cancer

Precision Medical Sciences ◽

10.1002/prm2.12039 ◽

2021 ◽

Author(s):

Zhuo Wang ◽

Changwen Jing ◽

Haixia Cao ◽

Jianzhong Wu ◽

Rong Ma

Keyword(s):

Thyroid Cancer ◽

Gene Mutations ◽

Chinese Patients ◽

Gnas Gene

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Gene Mutations in Epidermal Growth Factor Receptor Signaling Network and Their Association With Survival in Chinese Patients With Metastatic Colorectal Cancers

The Anatomical Record ◽

10.1002/ar.21202 ◽

2010 ◽

Vol 293 (9) ◽

pp. 1506-1511 ◽

Cited By ~ 8

Author(s):

Wangjun Liao ◽

Yulin Liao ◽

Jeff X. Zhou ◽

Jianming Xie ◽

Jinzhang Chen ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Growth Factor Receptor ◽

Gene Mutations ◽

Signaling Network ◽

Chinese Patients ◽

Colorectal Cancers ◽

Epidermal Growth ◽

Growth Factor Receptor Signaling

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Novel Recurrent Altered Genes in Chinese Patients With Anaplastic Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab014 ◽

2021 ◽

Author(s):

Lingyun Zhang ◽

Zhixiang Ren ◽

Zhengzheng Su ◽

Yang Liu ◽

Tian Yang ◽

...

Keyword(s):

Thyroid Cancer ◽

Copy Number ◽

Treatment Strategies ◽

Gene Mutations ◽

Anaplastic Thyroid Cancer ◽

Chinese Patients ◽

Driver Gene ◽

Phosphatidylinositol 3 Kinase ◽

Entire Cohort ◽

Whole Exome

Abstract Background Anaplastic thyroid cancer (ATC) is a rare but lethal malignancy, and few systematic investigations on genomic profiles of ATC have been performed in Chinese patients. Methods Fifty-four ATC patients in West China Hospital between 2010 to 2020 were retrospectively analyzed, while 29 patients with available samples were sequenced by whole-exome sequencing (WES). The associations between genomic alterations and clinical characteristics were statistically evaluated. Results The median overall survival was 3.0 months in the entire cohort, which was impacted by multiple clinical features, including age, tumor size, and different treatment strategies. In the WES cohort, totally 797 nonsilent mutations were detected; the most frequently altered genes were TP53 (48%), BRAF (24%), PIK3CA (24%), and TERT promoter (21%). Although these mutations have been well-reported in previous studies, ethnic specificity was exhibited in terms of mutation frequency. Moreover, several novel significantly mutated genes were identified including RBM15 (17%), NOTCH2NL (14%), CTNNA3 (10%), and KATNAL2 (10%). WES-based copy number alteration analysis also revealed a high frequent gain of NOTCH2NL (41%), which induced its increased expression. Gene mutations and copy number alterations were enriched in phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin (mTOR), NOTCH, and WNT pathways. Conclusions This study reveals shared and ethnicity-specific genomic profiles of ATC in Chinese patients and suggests NOTCH2NL may act as a novel candidate driver gene for ATC tumorigenesis.

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Clinical manifestations of familial exudative vitreoretinopathy in children with nucleotide sequence alterations in the FZD4 gene

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2021-14-4-52-59 ◽

2021 ◽

Vol 14 (4) ◽

pp. 52-59

Author(s):

L. A. Katargina ◽

V. V. Kadyshev ◽

E. V. Denisova ◽

E. A. Geraskina ◽

A. V. Marakhonov ◽

...

Keyword(s):

Nucleotide Sequence ◽

Direct Sequencing ◽

Molecular Genetic ◽

Clinical Manifestations ◽

Gene Mutations ◽

Interdisciplinary Approach ◽

Ophthalmological Examination ◽

Photographic Recording ◽

Familial Exudative Vitreoretinopathy ◽

National Medical

Familial exudative vitreoretinopathy (FEVR)is a rare genetically heterogeneous disease with multiple types of inheritance (autosomal dominant, autosomal recessive, X-linked) and widely varying clinical features. Up to 40 % of cases of FEVR are associated with mutations of the FZD4 gene.Purpose: to investigate the clinical manifestations of FEVR in children with nucleotide sequence alterations in the FZD4 gene. Material and methods. The Helmholtz National Medical ResearchCenter of Eye Diseases and the ResearchCentre for MedicalGenetics conducted a joint in-depth ophthalmological examination of 18 patients aged from 3 weeks to 17 years with a diagnosis of FEVR, which included a detailed ophthalmoscopy under drug mydriasis, ultrasound and electrophysiological examination, photographic recording of fundus changes using RetCam and Fundus Foto. Molecular genetic examination was carried out by direct sequencing according to Sanger. Results. Nucleotide sequence alterations in the FZD4 gene were detected in 3 patients(16.7 %)from two unrelated families. In one family, a 12-year-old girl wasfound to display the firstsymptoms of ophthalmic pathology (reduced vision, strabismus) at the age of 3.5 years. In another family, the clinical manifestations of FZD4 gene mutations were observed in two children during the first year of life (at the age of 5 and 11 months).Conclusions. The clinical picture of 3 patients with detected changes in the nucleotide sequence of the FZD4 gene is characterized by early manifestation and bilateral asymmetric ophthalmoscopic damage. The results of the study indicate the need for a timely diagnosis of FEVR in young children, recommend an interdisciplinary approach to the study of the disease, which should contribute to a better understanding of pathogenesis, and the development of an effective diagnostic, treatment and rehabilitation algorithm.

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Morphological and Genetic Heterogeneity of Synchronous Multifocal Lung Adenocarcinoma in a Chinese Cohort

10.21203/rs.3.rs-77421/v1 ◽

2020 ◽

Author(s):

Donglin Zhu ◽

Dan Cao ◽

Minghong Shen ◽

Jinghuan Lv

Keyword(s):

Lung Cancer ◽

Primary Lung Cancer ◽

Gene Mutations ◽

Tumor Location ◽

Chinese Patients ◽

Molecular Testing ◽

Additional Tool ◽

Molecular Features ◽

Pathologic Features ◽

Genotypic Analysis

Abstract Background: Synchronous multifocal lung cancer (SMLC) is seen with increasing frequency in clinical practice globally. Because of innate variation in clinical management and outcome, it is vital to distinguish properly between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Methods: We have collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumors were included in our study. The pathological features presented by these cases were analyzed, including tumor location, tumor size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We undertook molecular testing of nine driver oncogenes associated with lung cancer, including EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. Results: According to Martini-Melamed classification and refined standard, 8 and 17 cases were considered as SMPLC respectively. Gene mutations were identified in 18 tumors (36%). There were 12 patients had different gene mutations. Conclusions: We demonstrate that conventional morphological assessment is not sufficient to establish clearly the clonal relationship of SMPLC. Instead the evaluation of histological subtypes, including non-mucinous adherent components, is required. Multiplex genotypic analysis may also prove a useful additional tool.

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