title: Identification of a novel AluSx-mediated deletion of exon 3 in the SBDS gene in a patient with Shwachman-Diamond syndrome.
abstract: Shwachman-Diamond syndrome (SDS) is caused by mutations in the SBDS gene, most of which are the result of gene conversion events involving its highly homologous pseudogene SBDSP. Here we describe the molecular characterization of the first documented gross deletion in the SBDS gene, in a 4-year-old Portuguese girl with SDS. The clinical diagnosis was based on the presence of hematological symptoms (severe anemia and cyclic neutropenia), pancreatic exocrine insufficiency and skeletal abnormalities. Routine molecular screening revealed heterozygosity for the common splicing mutation c.258+2T>C, and a further step-wise approach led to the detection of a large deletion encompassing exon 3, the endpoints of which were subsequently delineated at the gDNA level. This novel mutation (c.258+374_459+250del), predictably giving rise to an internally deleted polypeptide (p.Ile87_Gln153del), appears to have arisen from an excision event mediated by AluSx elements which are present in introns 2 and 3. Our case illustrates the importance of including gross deletion screening in the SDS diagnostic setting, especially in cases where only one deleterious mutation is detected by routine screening methods. In particular, deletional rearrangements involving exon 3 should be considered, since Alu sequences are known to be an important cause of recurrent mutations.
authors: Escola Superior de Saúde, Instituto Politécnico de Bragança, Bragança, Portugal.
authors: Elísio
authors: E
authors: Costa
authors: Frederico
authors: F
authors: Duque
authors: Jorge
authors: J
authors: Oliveira
authors: Paula
authors: P
authors: Garcia
authors: Isabel
authors: I
authors: Gonçalves
authors: Luísa
authors: L
authors: Diogo
authors: Rosário
authors: R
authors: Santos
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D001855:Bone Marrow Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D005091:Exons; D005260:Female; D030342:Genetic Diseases, Inborn / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D007223:Infant; D010182:Pancreatic Diseases / Q000000981:diagnostic imaging; D017354:Point Mutation; D011174:Portugal; D011506:Proteins / Q000235:genetics*; D011859:Radiography; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D011506:Proteins; C470521:SBDS protein, human