Background: Schimke immuno-osseous dysplasia (SIOD) is a fatal autosomal recessive disorder caused by loss-of-function mutations in swi/snf-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1 (SMARCAL1).
Methods: Analysis of detailed autopsies to correlate clinical and pathological findings in two men severely affected with SIOD.
Results: As predicted by the clinical course, T cell deficiency in peripheral lymphoid organs, defective chondrogenesis, focal segmental glomerulosclerosis, cerebral ischaemic lesions and premature atherosclerosis were identified. Clinically unexpected findings included a paucity of B cells in the peripheral lymphoid organs, emperipolesis-like (penetration of one cell by another) abnormalities in the adenohypophysis, fatty infiltration of the cardiac right ventricular wall, pulmonary emphysema, testicular hypoplasia with atrophy and azospermia, and clustering of small cerebral vessels.
Conclusions: A regulatory role for the SMARCAL1 protein in the proliferation of chondrocytes, lymphocytes and spermatozoa, as well as in the development or maintenance of cardiomyocytes and in vascular homoeostasis, is suggested. Additional clinical management guidelines are recommended as this study has shown that patients with SIOD may be at risk of pulmonary hypertension, combined immunodeficiency, subcortical ischaemic dementia and cardiac dysfunction.
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- ARVCM, arrhythmogenic right ventricular cardiomyopathy
- CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy
- FSGS, focal segmental glomerulosclerosis
- H&E, haematoxylin and eosin
- SIOD, Schimke immuno-osseous dysplasia
- SMARCAL1, swi/snf-related matrix-associated actin-dependent regulator of chromatin, subfamily a-like 1
- TIA, transient ischaemic attack
Published Online First 13 July 2006
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