Relevance of SOX17 Variants for Hypomyelinating Leukodystrophies and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
Annals of Human Genetics. 2012-02-20; 76(3): 261-267
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1. Ann Hum Genet. 2012 May;76(3):261-7. doi: 10.1111/j.1469-1809.2011.00702.x. Epub
2012 Feb 20.
Relevance of SOX17 variants for hypomyelinating leukodystrophies and congenital
anomalies of the kidney and urinary tract (CAKUT).
Combes P(1), Planche V, Eymard-Pierre E, Sarret C, Rodriguez D, Boespflug-Tanguy
O, Vaurs-Barriere C.
(1)INSERM, UMR, CNRS, GReD, Medical School, Clermont-Ferrand, France.
The SRY-BOX17 gene (SOX17) encodes a transcription factor playing a key role in
different developmental processes including endoderm formation, cardiac
myogenesis, kidney/urinary development and differentiation of oligodendrocytes,
the brain myelinating cells. In a candidate gene approach, we analyzed the SOX17
gene in hypomyelinating leukodystrophies (HL) characterized by a permanent
deficit in the amount of central nervous system myelin. Five genes are involved
in the aetiology of HL but 40% of HL remains without known genetic origin (UHL).
New sequence variations in SOX17 were identified but all correspond to
nonpathogenic variants, suggesting that SOX17 is not involved in UHL phenotype.
In one patient, we identified the c.775T>A (p.Tyr259Asn) variation already
reported as causative of congenital kidney and urinary tract abnormalities
(CAKUT). Nevertheless, since our patient did not present such a phenotype, we
propose that this variant may alternatively represent an « at-risk » allele for
CAKUT rather than a causative allele. This observation strengthens the idea that
caution must be taken when linking genetic variation to disease, especially in
discrete phenotypes such as CAKUT.
© 2012 The Authors Annals of Human Genetics © 2012 Blackwell Publishing
Ltd/University College London.
PMID: 22348788 [Indexed for MEDLINE]