Purpose:Autosomal recessive congenital short bowel syndrome is caused by mutations in CLMP. No mutations were found in the affected males of a family with presumed X-linked congenital short bowel syndrome or in an isolated male patient. Our aim was to identify the disease-causing mutation in these patients.Methods:We performed mutation analysis of the second exon of FLNA in the two surviving affected males of the presumed X-linked family and in the isolated patient.Results:We identified a novel 2-base-pair deletion in the second exon of FLNA in all these male patients. The deletion is located between two nearby methionines at the N-terminus of filamin A. Previous studies showed that translation of FLNA occurs from both methionines, resulting in two isoforms of the protein. We hypothesized that the longer isoform is no longer translated due to the mutation and that this mutation is therefore not lethal for males in utero.Conclusion:Our findings emphasize that congenital short bowel syndrome can be the presenting symptom in male patients with mutations in FLNA.

FLNA, chronic idiopathic intestinal pseudo-obstruction, mutation, short small intestine, synovial lipomatosis
dx.doi.org/10.1038/gim.2012.123, hdl.handle.net/1765/39858
Genetics in Medicine
Erasmus MC: University Medical Center Rotterdam

van der Werf, C.S, Sribudiani, Y, Verheij, J.B, Carroll, M, O'Loughlin, E, Chen, C-H, … Hofstra, R.M.W. (2013). Congenital short bowel syndrome as the presenting symptom in male patients with FLNA mutations. Genetics in Medicine, 15(4), 310–313. doi:10.1038/gim.2012.123