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Mutation of CANT1 causes Desbuquois dysplasia
Author(s) -
Faden Maha,
AlZahrani Fatema,
Arafah Dia,
Alkuraya Fowzan S.
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33404
Subject(s) - genetics , disease gene identification , biology , hum , gene , renal dysplasia , concordance , mutation , exome sequencing , art , performance art , kidney , art history
Desbuquois dysplasia is an autosomal recessive dysplasia characterized by severe growth restriction and distinct hand and proximal femur appearance in addition to cognitive impairment. The critical interval for this disease has been mapped to 17q25.3 using homozygosity mapping. We have identified a newborn with classical features of the disease whose parents are first cousins. Assuming genetic homogeneity of this disorder, we were able to narrow the critical interval to a region that only contained 10 annotated genes by combining the results of our homozygosity mapping with those of others. Serial sequencing of the genes contained within the interval revealed a 5 bp duplication in Calcium‐Activated Nucleotidase 1 gene ( CANT1 ), consistent with the very recent report by Huber et al. [Huber et al. (2009); Am J Hum Genet 85:706–710]. This report cements the role of CANT1 in the causation of this dysplasia and demonstrates the high value of even single cases in the setting of genetically homogeneous disorders when homozygosity mapping is used. © 2010 Wiley‐Liss, Inc.