Shwachman–Bodian–Diamond syndrome
| Shwachman–Diamond syndrome | |
|---|---|
| Classification and external resources | |
| Specialty | medical genetics |
| ICD-10 | Q45.3 |
| OMIM | 260400 |
| DiseasesDB | 11894 |
| eMedicine | ped/2060 |
| MeSH | C537330 |
| GeneReviews | |
| Orphanet | 811 |
Shwachman–Diamond syndrome (SDS) or Shwachman–Bodian–Diamond syndrome is a rare congenital disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature. After cystic fibrosis (CF), it is the second most common cause of exocrine pancreatic insufficiency in children.
This syndrome shows a wide range of abnormalities and symptoms. The main characteristics of the syndrome are exocrine pancreatic dysfunction, hematologic abnormalities and growth retardation. Only the first two of these are included in the clinical diagnostic criteria.
Shwachman–Diamond syndrome is characterized by an autosomal recessive mode of inheritance. The gene that is mutated in this syndrome (SBDS) lies on the long arm of chromosome 7 at cytogenetic position 7q11. It is composed of five exons and has an associated mRNA transcript that is 1.6 kilobase pairs in length. The SBDS gene resides in a block of genomic sequence that is locally duplicated on the chromosome. The second copy contains a non-functional version of the SBDS gene that is 97% identical to the original gene, but has accumulated inactivating mutations over time. It is considered to be a pseudogene. In a study of 158 SDS families, 75% of disease-associated mutations appeared to be the result of gene conversion, while 89% of patients harbored at least one such mutation. Gene conversion occurs when the intact SBDS gene and its pseudogene copy aberrantly recombine at meiosis, leading to an incorporation of pseudogene-like sequences into the 'good copy' of the SBDS gene, thereby inactivating it. Two gene conversion mutations predominate; one is a splice site mutation affecting the 5' splice site of intron two, while the second is an exon two nonsense mutation.
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