☆ 4.5 Article

TMEM231 Gene Conversion Associated with Joubert and Meckel-Gruber Syndromes in the Same Family

HUMAN MUTATION (2016)

Journal

HUMAN MUTATION

Volume 37, Issue 11, Pages 1144-1148

Publisher

WILEY-BLACKWELL

DOI: 10.1002/humu.23054

Keywords

TMEM231; whole exome sequencing; translocation; gene conversion; cilia

Categories

Genetics & Heredity

Funding

Intramural Research Program of the National Human Genome Research Institute
National Institutes of Health (NIH)
NIH Medical Research Scholars Program
Pfizer Inc.
Doris Duke Charitable Foundation
Newport Foundation
American Association for Dental Research
Howard Hughes Medical Institute
Colgate-Palmolive Company

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

Joubert and Meckel-Gruber syndromes (JS and MGS) are ciliopathies with overlapping features. JS patients manifest the molar tooth sign on brain imaging and variable eye, kidney, and liver disease. MGS presents with polycystic kidneys, occipital encephalocele, and polydactyly; it is typically perinatally fatal. Both syndromes are genetically heterogeneous; some genes cause either syndrome. Here, we report two brothers married to unrelated women. The first brother had three daughters with JS and a son with polycystic kidneys who died at birth. The second brother's wife had a fetal demise due to MGS. Whole exome sequencing identified TMEM231 NM_001077416.2: c.784G>A; p.(Asp262Asn) in all children and the wife of the first brother; the second brother's wife had a c.406T>G;p.(Trp136Gly) change. In-depth analysis uncovered a rare gene conversion event in TMEM231, leading to loss of exon 4, in all the affected children of first brother. We believe that the combination of this gene conversion with different missense mutations led to a spectrum of phenotypes that span JS and MGS.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.5

Not enough ratings

Secondary Ratings

Novelty

-

Significance

-

Scientific rigor

-

Rate this paper

Recommended

Article Genetics & Heredity

Genetic profiles of non-syndromic severe-profound hearing loss in Chinese Hans by whole-exome sequencing

Ya Liu, Meihua Tan, Luhang Cai, Lihui Lv, Qingqing Chen, Wei Chen, Hang Yang, Yaping Xu

Summary: In this study, whole-exome sequencing was used to investigate the genetic causes of severe-profound hearing loss in Chinese Han children. Several novel genes and variants associated with hearing loss were identified, expanding our understanding of the heterogeneity of hereditary hearing loss.

GENE (2022)

Add to Collection

Article Cell Biology

Whole-Exome Sequencing Identifies a Novel CPT2 Mutation in a Pedigree With Gout

Yong Guo, Jing Jin, Zhenni Zhou, Yihui Chen, Li Sun, Chunwu Zhang, Xiaoru Xia

Summary: This study identified a rare CPT2 mutation in a large Chinese pedigree with gout. Functional studies revealed that the mutant protein induces protein degradation and affects the binding ability of CPT2 to UCP2. This study provides novel insight into the genetic etiology of gout.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

Add to Collection

Article Oncology

Patterns of Whole Exome Sequencing in Resected Cholangiocarcinoma

Lucas W. Thornblade, Paul Wong, Daneng Li, Susanne G. Warner, Sue Chang, Mustafa Raoof, Jonathan Kessler, Arya Amini, James Lin, Vincent Chung, Gagandeep Singh, Yuman Fong, Laleh G. Melstrom

Summary: Cholangiocarcinomas are rare cancers with potentially targetable mutations, and a third of patients undergoing resection in the past decade have had tumor genomic profiling, with 89% harboring targetable mutations. While targeted therapies were identified in most sequenced tumors, only 4% of patients received these therapies, highlighting the potential for precision medicine in the future care of cholangiocarcinoma.

CANCERS (2021)

Add to Collection

Article Genetics & Heredity

Whole-exome sequencing reveals genetic variants in low-risk and high-risk neuroblastoma

Zekiye Altun, Hongling Yuan, Burcin Baran, Safiye Aktas, Esra Esmeray Sonmez, Can Kucuk, Nur Olgun

Summary: This study aimed to investigate genetic aberrations in neuroblastoma (NB) by comparing high and low-risk NB patients using whole-exome sequencing (WES) and to reveal the heterogeneity and association between somatic variants and clinical features. Seven NB patients with clinical data were included (4 in the low-risk group and 3 in the high-risk group). Somatic variants associated with NB genes were identified and analyzed using bioinformatics methods. Several gene variations were found in both groups, including oncogenes and tumor suppressor genes. Candidate gene variations were associated with chromatin remodeling complexes, the RAS pathway, cell proliferation, and DNA repair mechanism. Some variations were specific to high-risk patients or low-risk patients. Comparisons with the cBioportal cancer genomic database identified common gene variants in high-risk patients but not in low-risk patients. GO/KEGG enrichment analysis was performed to explore relevant biological processes and molecular pathways related to gene variants, which can help unravel the molecular mechanisms of NB tumorigenesis and the phenotypic differences between high-risk and low-risk patients.

GENE (2023)

Add to Collection

Article Immunology

The Application of Whole-Exome Sequencing in Patients With FUO

Wanru Guo, Xuewen Feng, Ming Hu, Yanwan Shangguan, Jiafeng Xia, Wenjuan Hu, Xiaomeng Li, Zunjing Zhang, Yunzhen Shi, Kaijin Xu

Summary: The study found that the use of whole exome sequencing in patients with FUO can improve genetic diagnosis and treatment. In this study, positive results were found in 7 out of 15 sequenced samples, involving eight different genes.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2022)

Add to Collection

Article Chemistry, Multidisciplinary

Exploring the Genetic Basis of Dens Evaginatus Using Whole-Exome Sequencing

Heetae Park, Kazuyoshi Hosomichi, Yong-Il Kim, Atsushi Tajima, Tetsutaro Yamaguchi

Summary: This study used whole-exome sequencing (WES) to investigate the genetic background of dental abnormality called dens evaginatus (DE). The study identified gene variants of TLR3 and MDC1 as etiologic factors for DE. The findings contribute to understanding the etiology of DE and can potentially improve treatment and preventive measures, as well as aid in the development of regenerative medicine and gene therapy strategies.

APPLIED SCIENCES-BASEL (2022)

Add to Collection

Article Medicine, General & Internal

Identification of a wide spectrum of ciliary gene mutations in nonsyndromic biliary atresia patients implicates ciliary dysfunction as a novel disease mechanism

Wai-Yee Lam, Clara Sze-Man Tang, Man-Ting So, Haibing Yue, Jacob Shujui Hsu, Patrick Ho-Yu Chung, John M. Nicholls, Fanny Yeung, Chun-Wai Davy Lee, Diem Ngoc Ngo, Pham Anh Hoa Nguyen, Hannah M. Mitchison, Dagan Jenkins, Christopher O'Callaghan, Maria-Merce Garcia-Barcelo, So-Lun Lee, Pak-Chung Sham, Vincent Chi-Hang Lui, Paul Kwong-Hang

Summary: The study identified rare deleterious ciliary gene mutations in 31.5% of nonsyndromic BA patients. Functional analysis showed absence of cilia in BA livers with KIF3B and TTC17 mutations, and knockdown of PCNT, KIF3B and TTC17 resulted in reduced number of cilia in patients. Additionally, engineered zebrafish knockouts of KIF3B, PCNT and TTC17 displayed reduced biliary flow.

EBIOMEDICINE (2021)

Add to Collection

Article Pediatrics

Detection of DZIP1L mutations by whole-exome sequencing in consanguineous families with polycystic kidney disease

Jens Michael Hertz, Per Svenningsen, Henrik Dimke, Morten Buch Engelund, Hanne Norgaard, Anita Hansen, Niels Marcussen, Helle Charlotte Thiesson, Carsten Bergmann, Martin J. Larsen

Summary: We identified two different homozygous DZIP1L sequence variants: c.193 T > C; p.(Cys65Arg), and c.216C > G; p.(Cys72Trp) in four children with polycystic kidney disease. Functional analysis showed that the c.216C > G; p.(Cys72Trp) variant caused mislocalization of mutant DZIP1L. Our results suggest that the N-terminal domain plays a critical role in protein function. Including DZIP1L in multigene panels and whole-exome sequencing analysis is important for the diagnosis of cystic kidney diseases.

PEDIATRIC NEPHROLOGY (2022)

Add to Collection

Article Medicine, General & Internal

Genetic Aspects of Small for Gestational Age Infants Using Targeted-Exome Sequencing and Whole-Exome Sequencing: A Single Center Study

Su-Jung Park, Narae Lee, Seong-Hee Jeong, Mun-Hui Jeong, Shin-Yun Byun, Kyung-Hee Park

Summary: The prevalence of genetic causes in SGA infants without known risk factors was 22%, and targeted-panel sequencing or whole-exome sequencing was effective in diagnosing the etiology of SGA infants without a known cause.

JOURNAL OF CLINICAL MEDICINE (2022)

Add to Collection

Article Rheumatology

Whole exome sequencing in unclassified autoinflammatory diseases: more monogenic diseases in the pipeline?

Can Kosukcu, Ekim Z. Taskiran, Ezgi Deniz Batu, Erdal Sag, Yelda Bilginer, Mehmet Alikasifoglu, Seza Ozen

Summary: In this study, phenotype-genotype correlations in unclassified autoinflammatory disease (AID) patients were investigated using whole exome sequencing (WES), revealing disease-causing genetic variants in a subset of patients. The WES strategy proved to be cost-effective and yielded substantial results for the undefined AID patients, contributing to the understanding of the spectrum of unclassified AIDs.

RHEUMATOLOGY (2021)

Add to Collection

Article Genetics & Heredity

Case Report: Whole Exome Sequencing Revealed Two Novel Mutations of PIEZO1 Implicated in Nonimmune Hydrops Fetalis

Yuan Chen, Ying Jiang, Bangwu Chen, Yeqing Qian, Jiao Liu, Mengmeng Yang, Baihui Zhao, Qiong Luo

Summary: Nonimmune hydrops fetalis is a serious fetal condition that can be diagnosed prenatally by ultrasound, but determining the underlying etiology remains a challenge. Whole exome sequencing revealed mutations in the PIEZO1 gene related to NIHF, with potential positive impact on prognosis assessment.

FRONTIERS IN GENETICS (2021)

Add to Collection

Article Biochemistry & Molecular Biology

New Candidates for Autism/Intellectual Disability Identified by Whole-Exome Sequencing

Lucia Pia Bruno, Gabriella Doddato, Floriana Valentino, Margherita Baldassarri, Rossella Tita, Chiara Fallerini, Mirella Bruttini, Caterina Lo Rizzo, Maria Antonietta Mencarelli, Francesca Mari, Anna Maria Pinto, Francesca Fava, Alessandra Fabbiani, Vittoria Lamacchia, Anna Carrer, Valentina Caputo, Stefania Granata, Elisa Benetti, Kristina Zguro, Simone Furini, Alessandra Renieri, Francesca Ariani

Summary: Intelectual disability (ID) and autism spectrum disorder (ASD) are often associated and characterized by impairments in cognitive processes and daily life tasks. Molecular diagnosis is crucial for improving prognosis and initiating treatment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Add to Collection

Article Rheumatology

Ultra-rare genetic variation in relapsing polychondritis: a whole-exome sequencing study

Yiming Luo, Marcela A. Ferrada, Keith A. Sikora, Cameron Rankin, Hugh D. Alessi, Daniel L. Kastner, Zuoming Deng, Mengqi Zhang, Peter A. Merkel, Virginia B. Kraus, Andrew S. Allen, Peter C. Grayson

Summary: This study suggests that rare variants in the DCBLD2 gene may play a role in the development of RP. These findings should be further validated in a larger sample and supported by functional experiments.

ANNALS OF THE RHEUMATIC DISEASES (2023)

Add to Collection

Article Biotechnology & Applied Microbiology

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A

Muhammad Umair, Oliva Palander, Muhammad Bilal, Bader Almuzzaini, Qamre Alam, Farooq Ahmad, Muhammad Younus, Amjad Khan, Ahmed Waqas, Misbahuddin M. Rafeeq, Majid Alfadhel

Summary: Polydactyly or hexadactyly often involves various gene variants, and this study reveals the significant role of the DACH1 gene in human digit development, which remains largely unexplored.

GENOMICS (2021)

Add to Collection

Article Obstetrics & Gynecology

Whole exome sequencing in unexplained recurrent miscarriage families identified novel pathogenic genetic causes of euploid miscarriage

Xiyao Wang, Wenqiang Shi, Shaotong Zhao, Deshun Gong, Shuo Li, Cuiping Hu, Zi-Jiang Chen, Yan Li, Junhao Yan

Summary: This study utilized whole exome sequencing (WES) followed by trio bioinformatics analysis to identify genetic variants in six candidate genes that may be responsible for first trimester euploid miscarriage.

HUMAN REPRODUCTION (2023)

Add to Collection

Article Genetics & Heredity

Mutations in human homologue of chicken talpid3 gene (KIAA0586) cause a hybrid ciliopathy with overlapping features of Jeune and Joubert syndromes

May Christine V. Malicdan, Thierry Vilboux, Joshi Stephen, Dino Maglic, Luhe Mian, Daniel Konzman, Jennifer Guo, Deniz Yildirimli, Joy Bryant, Roxanne Fischer, Wadih M. Zein, Joseph Snow, Meghana Vemulapalli, James C. Mullikin, Camilo Toro, Benjamin D. Solomon, John E. Niederhuber, William A. Gahl, Meral Gunay-Aygun

JOURNAL OF MEDICAL GENETICS (2015)

Add to Collection

Article Genetics & Heredity

Cystic cerebellar dysplasia and biallelic LAMA1 mutations: a lamininopathy associated with tics, obsessive compulsive traits and myopia due to cell adhesion and migration defects

Thierry Vilboux, May Christine V. Malicdan, Yun Min Chang, Jennifer Guo, Patricia M. Zerfas, Joshi Stephen, Andrew R. Cullinane, Joy Bryant, Roxanne Fischer, Brian P. Brooks, Wadih M. Zein, Edythe A. Wiggs, Christopher K. Zalewski, Andrea Poretti, Melanie M. Bryan, Meghana Vemulapalli, James C. Mullikin, Martha Kirby, Stacie M. Anderson, Marjan Huizing, Camilo Toro, William A. Gahl, Meral Gunay-Aygun

JOURNAL OF MEDICAL GENETICS (2016)

Add to Collection

Meeting Abstract Clinical Neurology

A novel inborn error of the Coenzyme Q10 biosynthesis pathway: cerebellar ataxia and static encephalomyopathy due to COQ5 C-Methyltransferase deficiency

M. Malicdan, T. Vilboux, B. Ben-Zeev, J. Guo, A. Eliyahu, B. Pode-Shakked, A. Dori, S. Kakani, S. Chandrasekharappa, C. Ferreira, N. Shelestovich, D. Marek-Yagel, H. Pri-Chen, I. Blat, J. Niederhuber, C. Toro, J. Deeken, T. Yardeni, D. Wallace, W. Gahl, Y. Anikster

NEUROMUSCULAR DISORDERS (2017)

Add to Collection

Review Genetics & Heredity

O-GlcNAc: Regulator of Signaling and Epigenetics Linked to X-linked Intellectual Disability

Daniel Konzman, Lara K. Abramowitz, Agata Steenackers, Mana Mohan Mukherjee, Hyun-Jin Na, John A. Hanover

FRONTIERS IN GENETICS (2020)

Add to Collection

Article Multidisciplinary Sciences

Nutrient sensing pathways regulating adult reproductive diapause in C. elegans

Moriah Eustice, Daniel Konzman, Jeff M. Reece, Salil Ghosh, Jhullian Alston, Tyler Hansen, Andy Golden, Michelle R. Bond, Lara K. Abramowitz, John A. Hanover

Summary: Genetic and environmental manipulations can improve health span and lifespan, but the underlying mechanisms of diet-associated pro-longevity are not well understood. In a model organism, ARD is regulated by fatty acid metabolism, energy sensing, stress response, and insulin-like signaling, uncovering conserved genetic pathways required for ARD entry and recovery.

PLOS ONE (2022)

Add to Collection

No Data Available

© Peeref 2019-2024. All rights reserved.