Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Lipoid proteinosis (Lipoid proteinosis) - Gen ECM1

Lipoid proteinosis is a disease that results in the formation of numerous small deposits of proteins and other molecules in various tissues throughout the body. These tiny deposits occur on the skin, upper respiratory tract, the moist tissues lining the holes of the body (such as eyelids and mucous membranes), and other areas.

The first symptom of this disease is usually a hoarse voice, which is due to deposits on the vocal cords. In childhood this symptom is expressed as a weak cry. Voice anomalies persist throughout life and ultimately can cause difficulty speaking or complete loss of expression. The implication of the throat, tonsils and lips, can cause breathing problems and infections of the upper respiratory tract. Deposits on the tongue can lead to a thick and shorter tongue. They can also thicken the frenulum, so it may be difficult to extend the language. The tongue can also have a smooth appearance due to damage to the taste buds.

A characteristic feature of Lipoid proteinosis is the presence of multiple small bumps in the form of beads, which covers the top and bottom along the lash line eyelids. These bumps are called moniliforme blefarosis. They can cause irritation or itching in the eyeball, but generally do not alter the vision. Often, the skin and mucous membranes become fragile in children with lipoid proteinosis, resulting in bleeding and crusting after minor trauma. Often, these problems appear in childhood, first in the mouth, face and extremities. Eventually, these blisters form scabs and scars. Deposits accumulate in the skin, which causes the skin to become thicker and yellowish. Damage to the skin appear more frequently in areas exposed to friction, such as hands, elbows, knees, buttocks and armpits. Also, some people with this condition suffer from alopecia on the scalp, eyelashes and eyebrows.

This disease can also affect neurological functions, so some affected individuals may suffer from epilepsy or neurological and behavioral problems, which can include headaches, aggressive behavior, paranoia, hallucinations, loss of short term memory and fearlessness . It is believed that these characteristics are associated with calcification in the temporal lobes. Brain abnormalities and neurological characteristics not always occur at the same time, so that the cause of neurological characteristics is still unclear. Deposits can be found in some internal organs including the stomach, duodenum and colon. Deposits in these tissues usually cause no symptoms and may disappear with time.

This process is due to mutations in the ECM1 gene (extracellular matrix protein 1), located on the long arm of chromosome 1 (1q21), encoding a protein found in most tissues within the extracellular matrix. The ECM1 protein can bind numerous structural protein is involved in growth and cell differentiation, including keratinocytes. Protein can also regulate angiogenesis. Four isoforms are encoded protein ECM1 from ECM1 gene. These isoforms vary in length and in tissues where they are. The most abundant and widespread version is known as ECM1a.

Have been described at least 55 ECM1 gene mutations in people with lipoid proteinosis, of which: missense mutations (24), and cutting mutations -splicing- connection (4), small deletions (11), small insertions ( 3) small indels (3), major deletions (1) and insertions / higher duplications (2). Generally, mutations that lead to the development of Lipoid proteinosis occur in exon 6 and exon 7 of the gene ECM1. A mutation that eliminates a single nucleotide in exon 6 of ECM1 (507delT) gene has been found in many people around the world. Another mutation that occurs in exon 7 of the gene is common in affected individuals in South Africa and results in a premature stop signal in the protein coding (Gln276Ter or Q276X). Mutations of genes ECM1 Lipoid proteinosis result cause the synthesis of a nonfunctional protein or inhibit any protein synthesis. Deficiency or absence of functional protein ECM1 reduces binding between ECM1 and other proteins, leading to an unstable extracellular matrix. Without adequate support of the extracellular matrix, cells skin and other tissues are weakened. However, the cause of deposits in the skin and other tissues is unclear. An unstable extracellular matrix can cause neighboring cells produce excess proteins and other materials. May, as this excess substance accumulates in tissues, the characteristic of developing Lipoid proteinosis deposits.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests in IVAMI: in IVAMI perform detection of mutations associated with lipoid proteinosis, by complete PCR amplification of the exons of the gene ECM1 and subsequent sequencing.


Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated card blood sample   desiccated (IVAMI can mail the card to deposit the blood sample).