SickKids

Paediatric Laboratory Medicine
Paediatric Laboratory Medicine
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Shwachman-Diamond Syndrome (SDS)

Background
Who should be tested?
Testing Methodology
Potential Outcomes & Interpretation of Test Results
Cautions
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Background

Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder with an incidence of 1 in 50,000 births. SDS affects many organs in the body and the symptoms may vary from individual to individual. The primary features of SDS include: bone marrow problems (leading to inadequate production of some types of blood cells), a defect in the pancreas (leading to difficulties in digesting food), skeletal abnormalities, and short stature. Other, secondary, features may affect some but not all people with SDS. People with SDS are at risk for serious, sometimes fatal, complications such as severe infections, bone marrow failure and acute myelogenous leukemia.

The SBDS gene at 7q11 has recently been found to be the causative gene for SDS A pseudogene, SBDS-P, exists within a distally duplicated region and shares 97% nucleotide sequence identity with the SBDS gene. A majority of SDS patients have mutations resulting from recombination and gene conversion between the SBDS and SBDS-P genes. The two common conversion mutations account for 75% of all SDS disease alleles.

The disease is present when a child receives two copies of a defective gene, one from each parent. Any person with one copy of the defective SDS gene is a SDS carrier. Carriers do not have, and will never develop, SDS. However, if two carriers wish to have children, there is a one in four chance (25%) that their baby will be born with SDS. There is a three in four chance (75%) that their baby will not have SDS.

Who should be tested

  • individuals clinically suspected of being affected with Shwachman-Diamond syndrome and their parents
  • individuals with a family history of Shwachman-Diamond syndrome, where the SDS mutations have been identified in the proband, to determine the carrier status of unaffected individuals
  • pregnancies at risk due to a family history of Shwachman-Diamond syndrome

Testing Methodology

This assay consists of two stages:

  1. A direct mutation detection assay is used to test proband samples for two recurrent mutations in exon 2 of the SBDS gene, c.183_184TA>CT and c.258+2T>C
  2. Samples submitted on SDS patients may require analysis using direct sequencing for rare mutations in the SBDS gene

Potential Outcomes & Interpretation of Test Results

Reason
for referral

SBDS Gene Mutations
allele 1 / allele 2

Explanation

carrier testing

none detected /
none detected

  • This individual is unlikely to be a carrier of Shwachman-Diamond syndrome.

carrier testing

mutation detected / none detected

  • This individual is a carrier of Shwachman-Diamond syndrome, and may transmit a mutation to offspring.

diagnosis

none detected /
none detected

  • This result does not support a diagnosis of Shwachman-Diamond syndrome.

diagnosis

mutation detected / none detected

  • This result is unable to confirm a diagnosis of Shwachman-Diamond syndrome.

diagnosis

mutation detected / mutation detected

  • This result confirms a diagnosis of Shwachman-Diamond syndrome.

Cautions

  • Current molecular testing will not detect all possible mutations in this gene. A negative result does not rule out the possibility that the individual carries a rare SDS mutation not detected in the assay.
  • If the patient has had successful bone marrow transplantation, the analysis of blood may not be appropriate. The analysis of a different sample type, which represents pre-transplant status, may be indicated.
  • Test results should be interpreted in the context of clinical findings, family history and other laboratory data.
  • This test was developed and its performance characteristics validated by the Molecular Genetics Laboratory at the Hospital for Sick Children. It has not been cleared or approved by the U.S. Food and Drug Administration. The FDA has determined that such clearance or approval is not necessary. This test is used for clinical urposes.

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