A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: phenotypic spectrum and structural study of FHL1 mutations.

Journal of the Neurological Sciences
Dong-Hui ChenThomas D Bird

Abstract

An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and...Continue Reading

References

Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jun 22, 2000·Molecular Cell Biology Research Communications : MCBRC·P T LoughnaC Brownson
Aug 19, 2004·American Journal of Medical Genetics. Part a·William B DobynsCarole Ober
Aug 2, 2006·Current Opinion in Chemical Biology·Amedeo Caflisch
Feb 16, 2008·The Journal of Clinical Investigation·Joachim SchesslCarsten G Bönnemann
Oct 28, 2008·Neuromuscular Disorders : NMD·Sherine ShalabyIchizo Nishino
Dec 18, 2008·Nature Chemical Biology·Fabrizio Chiti, Christopher M Dobson
Jan 28, 2009·Neurology·S ShalabyI Nishino
Jul 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Naresh ChennamsettyBernhardt L Trout
Aug 19, 2009·Neurology·B SchoserC Windpassinger
Sep 1, 2009·American Journal of Human Genetics·Lucie GueneauGisèle Bonne

❮ Previous
Next ❯

Citations

Jun 2, 2011·European Journal of Human Genetics : EJHG·Anna SarkozyVolker Straub
Apr 24, 2012·Human Molecular Genetics·Felix W FriedrichLucie Carrier
Mar 13, 2014·The Journal of Clinical Investigation·Maggie P Y LamPeipei Ping
Jan 13, 2016·BMC Evolutionary Biology·Alex Cagan, Torsten Blass
Dec 17, 2011·Seminars in Pediatric Neurology·Joachim SchesslBenedikt Schoser
Nov 10, 2015·The Journal of Clinical Investigation·Inka AlbrechtIngrid E Lundberg
Sep 21, 2011·American Journal of Medical Genetics. Part a·Andreas TzschachBarbara Oehl-Jaschkowitz
Nov 22, 2012·Muscle & Nerve·Tobias SchreckenbachKristl G Claeys
Jul 25, 2015·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·S JacksonH Reichmann
May 12, 2015·BioMed Research International·Li-Yen R HuAikaterini Kontrogianni-Konstantopoulos
Oct 3, 2014·Human Molecular Genetics·Valentina EmmanueleMichio Hirano
Aug 28, 2012·Circulation. Cardiovascular Genetics·Josepha S BinderChristian Windpassinger
Mar 1, 2012·Molecular and Cellular Biochemistry·Jing-Yu LeeHu-Hui Lee
Oct 23, 2019·Journal of Cellular Physiology·Shunshun HanHuadong Yin
Nov 6, 2012·International Journal of Oncology·Kazuyuki KoikeKatsuhiro Uzawa
Sep 28, 2018·Human Molecular Genetics·Akatsuki KubotaMichio Hirano
Oct 15, 2020·Antioxidants·Judith Cantó-SantosGlòria Garrabou
Dec 17, 2020·International Journal of Molecular Sciences·Mai Thi NguyenWan Lee
Apr 14, 2021·Neuromuscular Disorders : NMD·Lei ChenZhi-Ying Wu

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.