Shwachman-Diamond syndrome ... (Shwachman-Diamond syndrome) - Gen SBDS.  

   The Shwachman-Diamond syndrome is an inherited disorder that affects many parts of the body, particularly bone marrow, pancreas and skeletal system. In Shwachman-Diamond syndrome, the malfunction of bone marrow cause the absence of some or all types of white blood cells. The shortage of neutrophils, causing neutropenia. Most people with Shwachman-Diamond syndrome have episodes of neutropenia, which makes them more vulnerable to infections such as pneumonia, otitis media, and infections of the skin. Less often, abnormalities of the bone marrow leading to anemia or thrombocytopenia, which can lead to bruising and abnormal bleeding.

People with this syndrome have an increased risk of several serious complications related to the malfunction of your bone marrow. In particular, have a higher probability to develop myelodysplastic syndrome (MDS) and aplastic anemia, disorders involving blood cell production as well as acute myeloid leukemia (AML).

The Shwachman-Diamond syndrome also affects the pancreas. In most infants syndrome, pancreas insufficiency occurs. Infants with pancreatic insufficiency have trouble digesting food and absorbing nutrients needed for growth. As a result, often they have steatorrhea and malnutrition. Pancreatic insufficiency often improves with age.

Another common feature is the skeletal abnormalities. Many affected individuals have problems with bone formation and growth, which most commonly affects the hips and knees. Low bone density causes some infants born with a ribcage and narrow ribs, which can cause respiratory problems, sometimes fatal. Complications of this disorder can affect other parts of the body, including the heart, eyes, teeth and skin. In addition, this syndrome may be associated with delayed speech and delayed development of motor skills such as sitting, standing and walking.

This process is due to mutations in the SBDS gene, located on the long (q) arm of chromosome 7 at position 11.21 (7q11.21), encoding a protein whose function is unknown, although it is active in cells throughout the body. It is thought that the protein may play a role in RNA processing. This protein may also be involved in the formation of ribosomes. In cases where not found any SBDS gene mutation, the cause of this disorder is unknown.

We found at least 20 mutations in the SBDS gene, causing Shwachman-Diamond syndrome. Most of these mutations are the result of an exchange of genetic material between the SBDS gene and a piece of DNA called pseudogene, located near the gene on chromosome 7. The genetic material pseudogene contains errors, when introduced in the SBDS gene, alter the way that encodes the protein. The two most common mutations in people with this syndrome are the result of exchanges between the SBDS gene and the nearby pseudogene. One of these mutations, 258 + 2T> C, nucleotide change in a region of intron 2. This mutation prevents production of any functional protein encoded by the gene. The other common mutation, 183-184TA> CT changes two nucleotides in the SBDS gene. This genetic change introduces a premature stop signal in encoding the protein. It is unclear whether this mutation leads to an abnormal protein shortened or prevents síntsis of any protein.

This disease is inherited in an autosomal recessive pattern, that is, 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 Shwachman-Diamond syndrome, by complete PCR amplification of the exons of the SBDS gene, and subsequent sequencing.

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