MUTATION IN BRIEF
HUMAN MUTATION Mutation in Brief #487 (2002) Online
© 2002 WILEY-LISS, INC.
Received 19 September 2001; accepted 21 December 2001.
Identification of a Novel NOG Gene Mutation (P35S)
in an Italian Family with Symphalangism
M. Mangino1, E. Flex1, M.C. Digilio2, A. Giannotti2, and B. Dallapiccola1
1C.S.S. Mendel Institute and University La Sapienza, Rome, Italy; 2Division of Medical Genetics Bambino Gesù
Hospital, Rome, Italy.
*Correspondence to: Prof. Bruno Dallapiccola, C.S.S. Mendel Institute Viale R. Margherita 261, 00198 Rome,
Italy; Tel.: +390644160503; Fax: +390644160548; E-mail: email@example.com
Communicated by Richard G. H. Cotton
Symphalangism (SYM or SYM1) is an autosomal dominant disorder characterized by
multiple joint fusions. The disease is caused by mutations of the NOG gene, that maps to
chromosome 17q22. So far, only six independent NOG mutations have been identified. We
have analysed an Italian family in which father and son had bilateral symphalangism and
detected a novel NOG mutation (P35S), originated in the father from a c.914C>T transition.
A different mutation in the same codon (P35R) has been previously described. Comparison
between different noggin gene hortologs shows that codon 35 is conserved. Therefore, this
codon should play an important role in NOG gene function. This is the first mutation
described for NOG after the initial report of NOG mutations being causative of SYM. © 2002
KEY WORDS: Noggin; NOG; Symphalangism; SYM1; joint malformation
Symphalangism (SYM1; OMIM 185800) is an autosomal dominant disorder characterized by early onset
progressive ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion (Cushing, 1916), and
conductive hearing loss (Vesell, 1960). In 1995, the SYM1 locus was mapped to chromosome 17q21-22
(Polymeropoulos et al., 1995). Subsequently, Gong et al. (1999) identified five familial noggin gene (NOG; OMIM
602991) mutations segregating with proximal symphalangism, and a de novo mutation in a patient with unaffected
parents. These authors also described a NOG mutation in a family with multiple synostoses syndrome (SYNS1;
OMIM 186500), demonstrating that SYM1 and SYNS1 are allelic disorders. All the seven NOG mutations
described so far alter evolutionarily conserved amino acid residues (Gong et al., 1999). Here we report a novel
mutation in the NOG gene segregating in two generations of an Italian family with symphalangism.
MATERIALS AND METHODS
We analysed an Italian family (Fig. 1) in which father and son had bilateral symphalangism of fingers 2-5 and
toes 3-4, short first metacarpals, distal hand phalangeal hypoplasia, and mild conductive hearing loss. The father
had also thoraco-lumbar scoliosis. Facial appearance was unremarkable in both patients.