CMT and CVT HOXD10 gene mutations

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J Orthop Res. 2006 Jan 31

HOXD10 M319K mutation in a family with isolated congenital vertical

talus.

Dobbs MB, Gurnett CA, Pierce B, Exner GU, Robarge J, Morcuende JA,

Cole WG, Templeton PA, B, Bowcock AM.

Department of Orthopedic Surgery, Washington University School of

Medicine, One Child Place, Suite 45 Saint Louis, Missouri 63110.

Congenital vertical talus (CVT) is a primary dislocation of the

talonavicular joint that often occurs in neuromusculoskeletal

syndromes, but may also be seen as an isolated abnormality. Six

families with isolated CVT were ascertained. DNA was isolated from 21

affected individuals and 17 unaffected individuals from these

families, as well as from five sporadic patients with CVT. Variable

expressivity was noted in three families, manifesting as clubfoot in

three individuals. Genome-wide linkage analysis generated a maximum

two-point logarithm of odds score on chromosome 2q with D2S1353 (Z

(max) = 1.43 at theta(max) = 0.1), 17 Mb from the HOXD gene cluster.

DNA from one affected individual of each family was subjected to

mutational analysis of the HOXD10 gene. A single missense mutation

was identified (M319K, 956T > A) in the homeodomain recognition helix

of the HOXD10 gene that segregated with disease in one large British

family. This mutation was recently described in a family of Italian

descent with CVT and Charcot-Marie-Tooth deformity HOXD10 gene

mutations were not identified in any of the other families or

sporadic patients with CVT, suggesting that genetic heterogeneity

underlies this disorder.