LMNA-related congenital muscular dystrophy

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LMNA-related congenital muscular dystrophy
Other namesCongenital muscular dystrophy due to LMNA mutation
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Specialty Neurology   OOjs UI icon edit-ltr-progressive.svg

Lamin A/C congenital muscular dystrophy (CMD) (L-CMD, congenital muscular dystrophy associated to the LMNA gene or Emery-Dreifuss muscular dystrophy II) is a disease that it is included in laminopathies. Laminopathies are caused, among other mutations, to mutations in LMNA, a gene that synthesizes lamins A and C.

Contents

Currently there are approximately 200 cases worldwide.

This illness implies, like other muscular dystrophies, muscle weakness, motor difficulties and lack of control in the movement of the head, respiratory failure and cardiac abnormalities and symptoms are usually evident before the age of 2.

It can be an autosomal dominant inherited disease that affects both male and female but most known cases are de-novo mutations (spontaneous mutation) and are therefore not inherited. It is dominantly inherited because the abnormal gene would dominate beyond the normal one and it would transmit the disease. But it can also be recessive inheritance, which means that parents would carry the disease but it would not appear.Therefore, although parents have normal genes, children who are affected by mutations will have kids that would suffer the same disease as it is transmitted through heredity. This dystrophy was discovered thanks to geneticist, Gisèle Bonne, who identified the first mutation of the LMNA gene in 1999.

Symptoms

In general, the symptoms are:

Genetics

Mutations on this gene are responsible for congenital muscular dystrophy (CMD), overlapping syndromes related to mutation have also been reported. It is located on the long arm of the chromosome 1 (1q21-q22) and encodes the proteins lamin A and lamin C. [1] These are structural proteins of intermediate filaments that provide stability and strength to the cells. They play an important role in the organization of chromatin and nuclear membrane. [2] A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in non-homologous end joining and homologous recombination, processes that repair DNA double-strand breaks. [3]

Diagnosis

Unlike most muscular dystrophies, lamin A/C CMD does not present a breakdown of muscular fibres caused by muscle degeneration.

The only certain way to diagnose this disease is with molecular techniques like LMNA gene sequencing.

Treatment

There is no cure for CMD. Symptoms are managed for each individual and may involve the coordination of several healthcare specialists. [4]

Prognosis

There is an open prognosis because this disease has an unknown evolution. The cure of the disease could be found through some advanced therapies such as CRISPR/Cas9.

See also

Related Research Articles

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<span class="mw-page-title-main">Progeria</span> Genetic disorder that causes early aging

Progeria is a specific type of progeroid syndrome, also known as Hutchinson–Gilford syndrome. A single gene mutation is responsible for progeria. The gene, known as lamin A (LMNA), makes a protein necessary for holding the nucleus of the cell together. When this gene gets mutated, an abnormal form of lamin A protein called progerin is produced. Progeroid syndromes are a group of diseases that causes individuals to age faster than usual, leading to them appearing older than they actually are. Patients born with progeria typically live to an age of mid-teens to early twenties.

<span class="mw-page-title-main">Limb–girdle muscular dystrophy</span> Medical condition

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<span class="mw-page-title-main">Lamin</span>

Lamins, also known as nuclear lamins are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. Lamins have elastic and mechanosensitive properties, and can alter gene regulation in a feedback response to mechanical cues. Lamins are present in all animals but are not found in microorganisms, plants or fungi. Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. Mutations in lamin genes can result in several genetic laminopathies, which may be life-threatening.

<span class="mw-page-title-main">Becker muscular dystrophy</span> Genetic muscle disorder

Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, but has a milder course.

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<span class="mw-page-title-main">Fukuyama congenital muscular dystrophy</span> Medical condition

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Nemaline myopathy is a congenital, often hereditary neuromuscular disorder with many symptoms that can occur such as muscle weakness, hypoventilation, swallowing dysfunction, and impaired speech ability. The severity of these symptoms varies and can change throughout one's life to some extent. The prevalence is estimated at 1 in 50,000 live births. It is the most common non-dystrophic myopathy.

<span class="mw-page-title-main">Mitochondrial myopathy</span> Medical condition

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<span class="mw-page-title-main">Emery–Dreifuss muscular dystrophy</span> Medical condition

Emery–Dreifuss muscular dystrophy (EDMD) is a type of muscular dystrophy, a group of heritable diseases that cause progressive impairment of muscles. EDMD affects muscles used for movement, causing atrophy, weakness and contractures. It almost always affects the heart, causing abnormal rhythms, heart failure, or sudden cardiac death. It is rare, affecting 0.39 per 100,000 people. It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.

<span class="mw-page-title-main">Myotonic dystrophy</span> Genetic disorder that impairs muscle function

Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often unable to relax after contraction. Other manifestations may include cataracts, intellectual disability and heart conduction problems. In men, there may be early balding and an inability to father children. While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s.

<span class="mw-page-title-main">Laminopathy</span> Medical condition

Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term nuclear envelopathies that was coined in 2000 for diseases associated with defects of the nuclear envelope. Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals.

<span class="mw-page-title-main">Bethlem myopathy</span> Medical condition

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<span class="mw-page-title-main">Prelamin-A/C</span> Filament protein

Prelamin-A/C, or lamin A/C is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins.

ZMPSTE24 is a human gene. The protein encoded by this gene is a metallopeptidase. It is involved in the processing of lamin A. Defects in the ZMPSTE24 gene lead to similar laminopathies as defects in lamin A, because the latter is a substrate for the former. In humans, a mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder. Failure to correctly process prelamin A leads to deficient ability to repair DNA double-strand breaks.

<span class="mw-page-title-main">Ullrich congenital muscular dystrophy</span> Medical condition

Ullrich congenital muscular dystrophy (UCMD) is a form of congenital muscular dystrophy. There are two forms: UCMD1 and UCMD2.

Progeroid syndromes (PS) are a group of rare genetic disorders that mimic physiological aging, making affected individuals appear to be older than they are. The term progeroid syndrome does not necessarily imply progeria, which is a specific type of progeroid syndrome.

Veena Krishnaji Parnaik is an Indian cell biologist and the current Chief Scientist at the Centre for Cellular and Molecular Biology. She obtained her Masters in Science in medicinal biochemistry from the University of Mumbai and received her PhD from Ohio State University before moving back to India to work at the CCMB. Her research is focused on understanding the functional role of the nuclear lamina and how defects in it may lead to disorders such as progeria and muscular dystrophy.

<span class="mw-page-title-main">Muscle–eye–brain disease</span> Medical condition

Muscle–eye–brain (MEB) disease, also known as muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3), is a kind of rare congenital muscular dystrophy (CMD), largely characterized by hypotonia at birth. Patients have muscular dystrophy, central nervous system abnormalities and ocular abnormalities. The condition is degenerative.

References

  1. Carboni N, Politano L, Floris M, Mateddu A, Solla E, Olla S, Maggi L, Antonietta Maioli M, Piras R, Cocco E, Marrosu G, Giovanna Marrosu M (May 2013). "Overlapping syndromes in laminopathies: a meta-analysis of the reported literature". Acta Myol. 32 (1): 7–17. PMC   3665370 . PMID   23853504.
  2. Lewin, Benjamin (2001). Genes VII (in Spanish). Madrid: Marbán Libros S.L.
  3. Redwood, Abena B.; Perkins, Stephanie M.; Vanderwaal, Robert P.; Feng, Zhihui; Biehl, Kenneth J.; Gonzalez-Suarez, Ignacio; Morgado-Palacin, Lucia; Shi, Wei; Sage, Julien; Roti-Roti, Joseph L.; Stewart, Colin L.; Zhang, Junran; Gonzalo, Susana (27 October 2014). "A dual role for A-type lamins in DNA double-strand break repair". Cell Cycle. 10 (15): 2549–2560. doi:10.4161/cc.10.15.16531. PMC 3180193. PMID   21701264
  4. Sparks SE. "Congenital Muscular Dystrophy". NORD. National Organization for Rare Disorders. Retrieved September 19, 2018.