A Novel GDF6 Mutation in a Family with Multiple Synostoses Syndrome without Hearing Loss.

ABSTRACT: A 4-generation family with multiple synostoses syndrome type 4 (SYNS4) is reported, the third family identified so far. The phenotype segregated with a previously undescribed Asn399Lys (c.1197C>A) substitution in GDF6. N399 is part of a hydrophobic pocket critical for binding the BMP/GDF antagonist noggin. The N399K substitution renders GDF6 more similar to noggin-resistant members of the BMP family, namely GDF2 and BMP10, both of which contain lysine in the corresponding position. To further define the SYNS4 phenotype, we examined 6 of 9 affected family members. The phenotype was carpal and tarsal synostoses with painful feet after walking, but the condition could also be asymptomatic. Interestingly, unlike the previous SYNS4 families, the family presented here has no history of he

SUBMITTER: Drage Berentsen R 

PROVIDER: S-EPMC6362854 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature