Laminopathies are a group of rare genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

s caused by mutation

Mutation

In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

s in genes encoding proteins of the nuclear lamina

Nuclear lamina

The nuclear lamina is a dense fibrillar network inside the nucleus of a eukaryotic cell. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division...

. They are included in the more generic term nuclear envelopathies that was coined in 2000 for diseases associated with defects of the nuclear envelope

Nuclear envelope

A nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...

. 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.

Symptoms

Laminopathies and other nuclear envelopathies have a large variety of clinical symptoms including skeletal and/or cardiac muscular dystrophy

Muscular dystrophy

Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...

, lipodystrophy

Lipodystrophy

Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...

 and diabetes, dysplasia

Dysplasia

Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...

, dermo- or neuropathy, leukodystrophy

Leukodystrophy

Leukodystrophy refers to a group of disorders characterized by dysfunction of the white matter of the brain. The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers...

, and progeria

Progeria

Progeria is an extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. The word progeria comes from the Greek words "pro" , meaning "before", and "géras" , meaning "old age"...

 (premature aging). Most of these symptoms develop after birth, typically during childhood or adolescence. Some laminopathies however may lead to an early death, and mutations of lamin B (LMNB1 gene) may be lethal before or at birth.

Genetics

Patients with classical laminopathy have mutations in the gene coding for lamin

Lamin

Nuclear lamins, also known as Class V intermediate filaments, are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with membrane-associated proteins to form the nuclear lamina on the interior of the nuclear envelope...

 A/C (LMNA

LMNA

Lamin A/C also known as LMNA is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins.-Function:...

 gene).

More recently, mutations in lamin B

Lamin B

Lamin B is a protein associated with laminopathies....

 (LMNB2 gene) or genetic defects leading to changes in lamin B abundance were identified as cause for laminopathies.

Mutations implicated in other nuclear envelopathies were found in genes coding for lamin-binding proteins such as lamin B receptor

Lamin B receptor

Lamin-B receptor is a protein that in humans is encoded by the LBR gene.-Clinical significance:There is evidence tying it to Greenberg dysplasia and Pelger-Huet anomaly.-Interactions:Lamin B receptor has been shown to interact with CBX3 and CBX5....

 (LBR gene), emerin

Emerin

Emerin, together with MAN1, is a LEM domain-containing integral membrane protein of the nuclear membrane in vertebrates. The function of MAN1 is not extensively known, but emerin is known to interact with nuclear lamins, barrier-to-autointegration factor , nesprin-1α, and a transcription...

 (EMD gene) and LEM domain-containing protein 3

LEM domain-containing protein 3

LEM domain-containing protein 3 is a membrane protein associated with laminopathies.It is also associated with osteopoikilosis.LEMD3 protein, also known as MAN1, is an inner nuclear membrane protein that was isolated from the serum of a patient with an autoimmune disease...

 (LEMD3 gene) and prelamin-processing enzymes such as the zinc metalloproteinase STE24

Zinc metalloproteinase STE24

Zinc metalloproteinase STE24 is a metalloproteinase enzyme associated with laminopathies....

 (ZMPSTE24 gene).

Mutations causing laminopathies include recessive as well as dominant allele

Allele

An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

s with rare de novo mutations creating dominant alleles that do not allow their carriers to reproduce before death.

The nuclear envelopathy with the highest frequency in human populations is Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy

Emery–Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement and heart muscle.It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.-Presentation:...

 caused by an X-linked

Sex linkage

Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance...

 mutation in the EMD gene coding for emerin and affecting an estimated 1 in 100,000 people.

Molecular action

Lamins are intermediate filament

Intermediate filament

Intermediate filaments are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of 7 nm actin , and that of 25 nm microtubules, although they were initially designated...

 proteins that form the nuclear lamina

Nuclear lamina

The nuclear lamina is a dense fibrillar network inside the nucleus of a eukaryotic cell. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division...

 scaffold underneath the nuclear envelope

Nuclear envelope

A nuclear envelope is a double lipid bilayer that encloses the genetic material in eukaryotic cells. The nuclear envelope also serves as the physical barrier, separating the contents of the nucleus from the cytosol...

 in animal cells. They are attached to the nuclear envelope membrane via farnesyl anchors and interaction with inner nuclear membrane proteins such as lamin B receptor and emerin. The nuclear lamina appears to be an adaptation to mobility in animals as sessile organisms such as plant

Plant

Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s or fungi

Fungus

A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 do not have lamins and the symptoms of many laminopathies include muscle

Muscle

Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...

 defects. Mutations in these genes might lead to defects in filament assembly and/or attachment to the nuclear envelope and thus jeopardize nuclear envelope stability in physically stressed tissues such as muscle fibers, bone

Bone

Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

, skin

Skin

-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

 and connective tissue

Connective tissue

"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...

.

Messenger RNA

Messenger RNA

Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...

 produced from the LMNA gene undergoes alternative splicing

Alternative splicing

Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 and is translated into lamins A and C. Lamin A undergoes farnesylation

Prenylation

Prenylation, or isoprenylation, or lipidation is the addition of hydrophobic molecules to a protein. It is usually assumed that prenyl groups facilitate attachment to cell membranes, similar to lipid anchor like the GPI anchor, though direct evidence is missing...

 to attach a membrane anchor to the protein. This version of the protein is also referred to as prelamin A. Farnesylated prelamin A is further processed

Posttranslational modification

Posttranslational modification is the chemical modification of a protein after its translation. It is one of the later steps in protein biosynthesis, and thus gene expression, for many proteins....

 into mature lamin A by a metalloproteinase

Metalloproteinase

Metalloproteinases constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some use...

 removing the last 15 amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s and its farnesylated cysteine

Cysteine

Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...

. This allows lamin A to dissociate from the nuclear envelope membrane and fulfill nuclear functions. Mutations causing laminopathies interfere with these processes on different levels.

Nonsense and missense mutations

Missense mutation

Missense mutation

In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...

s in the lamin A/C rod and tail domains are the cause for a wide array of genetic disorders, suggesting that lamin A/C protein contains distinct functional domains that are essential for the maintenance and integrity of different cell lineages. Interaction between lamin A and the nuclear envelope protein emerin appears to be crucial in muscle cells, with certain mutations in lamin mimicking mutations in emerin and causing Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy

Emery–Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement and heart muscle.It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.-Presentation:...

. Different mutations lead to dominant-negative and recessive alleles. Mutations in the lamin rod domain leading to mislocalization of both lamin A and emerin occur in patients with autosomal dominant forms of muscular dystrophy and cardiomyopathy.

Most lamin B mutations appear to be lethal with mutations in lamin B1 causing death at birth in mice. In 2006, lamin B2 missense mutations were identified in patients with acquired partial lipodystrophy.

Splicing defects

Mutations causing progeria

Progeria

Progeria is an extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. The word progeria comes from the Greek words "pro" , meaning "before", and "géras" , meaning "old age"...

 are defective in splicing

Splicing (genetics)

In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...

 LMNA mRNA, therefore producing abnormal lamin A protein, also known as progerin. The mutations activate a cryptic splice site within exon

Exon

An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...

 11 of the gene, thereby causing the deletion of the processing site on prelamin A. This results in an accumulation of progerin that is unable to mature into lamin A, leading to misshapen nuclei. Missplicing also leads to the complete or partial loss of exon 11 and results in a truncated prelamin A protein in the neonatal lethal tight skin contracture syndrome.

Processing defects

Since the metalloproteinase STE24 is required to process prelamin A into mature lamin A, mutations in this gene abolishing protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 activity cause defects similar to laminopathies caused by prelamin A with truncated processing sites. Symptoms in patients with ZMPSTE24 mutation range from mandibuloacral dysplasia, progeroid appearance, and generalized lipodystrophy to infant-lethal restrictive dermopathy.

Gene dosage effects

In the case of autosomal dominant leukodystrophy, the disease is associated with a duplication of the lamin B gene LMNB1. The exact dosage

Gene dosage

Gene dosage is the number of copies of a gene present in a cell or nucleus. An increase in gene dosage can cause higher levels of gene product if the gene is not subject to regulation from elsewhere in the body....

 of lamin B in cells appears to be crucial for nuclear integrity as increased expression of lamin B causes a degenerative phenotype in fruit flies

Drosophila

Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

 and leads to abnormal nuclear morphology.

Autoimmune antibodies

Antibodies against lamin B have been implicated in autoimmune disease

Autoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

s and are possibly involved in multiple sclerosis

Multiple sclerosis

Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

.

Treatment and drug development

Currently, there is no cure for laminopathies and treatment is largely symptomatic and supportive. Physical therapy

Physical therapy

Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...

 and/or corrective orthopedic surgery

Orthopedic surgery

Orthopedic surgery or orthopedics is the branch of surgery concerned with conditions involving the musculoskeletal system...

 may be helpful for patients with muscular dystrophies. Cardiac problems that occur with some laminopathies may require a pacemaker

Cardiac pacemaker

right|thumb|350px|Image showing the cardiac pacemaker which is the SA nodeThe contraction of heart muscle in all animals with hearts is initiated by chemical impulses. The rate at which these impulses fire controls the heart rate...

. Treatment for neuropathies may include medication for seizure

Seizure

An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s and spasticity

Spasticity

Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...

.

The recent progress in uncovering the molecular mechanisms of toxic progerin formation in laminopathies leading to premature aging has opened up the potential for the development of targeted treatment. The farnesylation of prelamin A and its pathological form progerin is carried out by the enzyme farnesyl transferase. Farnesyl transferase inhibitors (FTIs) can be used effectively to reduce symptoms in two mouse model systems for progeria and to revert the abnormal nuclear morphology in progeroid cell cultures. Two oral FTIs, lonafarnib

Lonafarnib

Lonafarnib is a farnesyl-OH-transferase inhibitor that is being investigated in a human clinical trial as a potential treatment for progeria....

 and tipifarnib

Tipifarnib

Tipifarnib is a farnesyltransferase inhibitor that is being investigated in patients 65 years of age and older with newly diagnosed acute myeloid leukemia . It inhibits the Ras kinase in a post translational modification step before the kinase pathway becomes hyperactive...

, are already in use as anti-tumor medication in humans and may become avenues of treatment for children suffering from laminopathic progeria. Nitrogen-containing bisphosphate drugs used in the treatment of osteoporosis

Osteoporosis

Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...

 reduce farnesyldiphosphate

Farnesyl pyrophosphate

Farnesyl pyrophosphate is an intermediate in the HMG-CoA reductase pathway used by organisms in the biosynthesis of terpenes, terpenoids, and sterols...

 production and thus prelamin A farnesylation. Testing of these drugs may prove them to be useful in treating progeria as well. The use of antisense oligonucleotide

Oligonucleotide

An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...

s to inhibit progerin synthesis in affected cells is another avenue of current research into the development of anti-progerin drugs.

List of known laminopathies and other nuclear envelopathies

Syndrome	OMIM ID	Symptoms	Mutation in	Identified in
Atypical Werner syndrome		Progeria Progeria Progeria is an extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. The word progeria comes from the Greek words "pro" , meaning "before", and "géras" , meaning "old age"...  with increased severity compared to normal Werner syndrome Werner syndrome Werner syndrome is a very rare, autosomal recessive disorder characterized by the appearance of premature aging....	Lamin A/C	2003
Barraquer-Simons syndrome Barraquer-Simons syndrome Barraquer–Simons syndrome is a rare form of lipodystrophy,which usually first affects the head, and then spreads to the thorax....		Lipodystrophy Lipodystrophy Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...	Lamin B	2006
Buschke-Ollendorff syndrome Buschke-Ollendorff syndrome Buschke–Ollendorff syndrome, also known as Dermatofibrosis lenticularis disseminata, is a rare genetic disorder associated with LEMD3. It is believed to be inherited in an autosomal dominant manner....		Skeletal dysplasia Dysplasia Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process... , skin lesions	LEM domain containing protein 3 (lamin-binding protein)	2004
	Cardiomyopathy Cardiomyopathy Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...	Lamin A/C	1999
Cardiomyopathy, dilated, with quadriceps myopathy		Cardiomyopathy Cardiomyopathy Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...	Lamin A/C	2003
Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease Charcot–Marie–Tooth disease- , known also as Morbus Charcot-Marie-Tooth, Charcot-Marie-Tooth neuropathy, hereditary motor and sensory neuropathy , hereditary sensorimotor neuropathy , or peroneal muscular atrophy, is an inherited disorder of nerves that takes different forms... , axonal, type 2B1		Neuropathy	Lamin A/C	2002
Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy Emery–Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement and heart muscle.It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.-Presentation:... , X-linked (EDMD)		Skeletal and cardiac muscular dystrophy Muscular dystrophy Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...	Emerin (lamin-binding protein)	1996, 2000
Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy Emery–Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement and heart muscle.It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.-Presentation:... , autosomal dominant (EDMD2)		Skeletal and cardiac muscular dystrophy Muscular dystrophy Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...	Lamin A/C	1999
Emery-Dreifuss muscular dystrophy Emery-Dreifuss muscular dystrophy Emery–Dreifuss muscular dystrophy is a condition that chiefly affects muscles used for movement and heart muscle.It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.-Presentation:... , autosomal recessive (EDMD3)		Skeletal and cardiac muscular dystrophy Muscular dystrophy Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...	Lamin A/C	2000
Familial partial lipodystrophy of the Dunnigan type (FPLD)		Lipoatrophic diabetes Lipoatrophic diabetes Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes....	Lamin A/C	2002
Greenberg dysplasia		Skeletal dysplasia Dysplasia Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...	Lamin B receptor	2003
Hutchinson-Gilford progeria syndrome (HGPS)		Progeria Progeria Progeria is an extremely rare genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. The word progeria comes from the Greek words "pro" , meaning "before", and "géras" , meaning "old age"...	Lamin A/C	2003
Leukodystrophy, demyelinating, adult-onset, autosomal dominant (ADLD)		Progressive demyelinating disorder affecting the central nervous system Central nervous system The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...	Lamin B (tandem gene duplication)	2006
Limb-girdle muscular dystrophy Limb-girdle muscular dystrophy Limb-girdle muscular dystrophy or Erb's muscular dystrophy is an autosomal class of muscular dystrophy that is similar but distinct from Duchenne muscular dystrophy and Becker's muscular dystrophy...  type 1B (LGMD1B)		Muscular dystrophy Muscular dystrophy Muscular dystrophy is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion. Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.In the 1860s, descriptions of boys who...  of hips and shoulders, cardiomyopathy Cardiomyopathy Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...	Lamin A/C	2000
Lipoatrophy with diabetes, hepatic steatosis, hypertrophic cardiomyopathy, and leukomelanodermic papules (LDHCP)		Lipoatrophic diabetes Lipoatrophic diabetes Lipoatrophic diabetes is a type of diabetes mellitus presenting with severe lipodystrophy in addition to the traditional signs of diabetes.... , fatty liver Fatty liver Fatty liver, also known as fatty liver disease , is a reversible condition where large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis... , hypertrophic cardiomyopathy Hypertrophic cardiomyopathy Hypertrophic cardiomyopathy is a disease of the myocardium in which a portion of the myocardium is hypertrophied without any obvious cause... , skin lesions	Lamin A/C	2003
Mandibuloacral dysplasia Mandibuloacral dysplasia Mandibuloacral dysplasia is a rare autosomal recessive syndrome characterized by mandibular hypoplasia, delayed cranial suture closure, dysplastic clavicals, abbreviated and club-shaped terminal phalanges, acroosteolysis, atrophy of the skin of the hands and feet, and typical facial changes.Types...  with type A lipodystrophy (MADA)		Dysplasia Dysplasia Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...  and lipodystrophy Lipodystrophy Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...	Lamin A/C	2002
Mandibuloacral dysplasia Mandibuloacral dysplasia Mandibuloacral dysplasia is a rare autosomal recessive syndrome characterized by mandibular hypoplasia, delayed cranial suture closure, dysplastic clavicals, abbreviated and club-shaped terminal phalanges, acroosteolysis, atrophy of the skin of the hands and feet, and typical facial changes.Types...  with type B lipodystrophy (MADB)		Dysplasia Dysplasia Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...  and lipodystrophy Lipodystrophy Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...	Zinc metalloprotease STE24 (prelamin-processing enzyme)	2003
Pelger-Huet anomaly Pelger-Huet anomaly Pelger-Huet anomaly is a blood laminopathy associated with the lamin B receptor.It is characterized by a white blood cell type known as a neutrophil whose nucleus is hyposegmented.It is a genetic disorder with an autosomal dominant inheritance pattern...  (PHA)		Myelodysplasia Myelodysplastic syndrome The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....	Lamin B receptor	2002
Pelizaeus-Merzbacher disease Pelizaeus-Merzbacher disease Pelizaeus–Merzbacher disease is a rare central nervous system disorder in which coordination, motor abilities, and intellectual function are delayed to variable extents.-Classification:... , adult-onset, autosomal dominant		Leukodystrophy Leukodystrophy Leukodystrophy refers to a group of disorders characterized by dysfunction of the white matter of the brain. The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers...	Lamin B	2006
Tight skin contracture syndrome, lethal		Dermopathy Dermopathy Dermopathy can refer to:* Diabetic dermopathy* Graves' dermopathy, or Infiltrative dermopathy* Nephrogenic fibrosing dermopathy * Restrictive dermopathyspecial type of diseases accouting with skin and its underlying layers...	Lamin A/C or Zinc metalloprotease STE24 (prelamin-processing enzyme)	2004

External links

• GeneReview/NIH/UW entry on LMNA-Related Dilated Cardiomyopathy