title: Identification of the gene for oral-facial-digital type I syndrome.
abstract: Oral-facial-digital type 1 syndrome (OFD1 [MIM 311200]) is transmitted as an X-linked dominant condition with lethality in males and is characterized by malformations of the face, oral cavity, and digits, and by a highly variable expressivity even within the same family. Malformation of the brain and polycystic kidneys are commonly associated with this disorder. The locus for OFD1 was mapped by linkage analysis to a 12-Mb interval, flanked by markers DXS85 and DXS7105 in the Xp22 region. To identify the gene responsible for this syndrome, we analyzed several transcripts mapping to the region and found mutations in OFD1 (formerly named "Cxorf5/71-7a"), encoding a protein containing coiled-coil alpha-helical domains. Seven patients with OFD1, including three with familial and four with sporadic cases, were analyzed. Analysis of the familial cases revealed a missense mutation, a 19-bp deletion, and a single base-pair deletion leading to a frameshift. In the sporadic cases, we found a missense (de novo), a nonsense, a splice, and a frameshift mutation. RNA in situ studies on mouse embryo tissue sections show that Ofd1 is developmentally regulated and is expressed in all tissues affected in OFD1 syndrome. The involvement of OFD1 in oral-facial-digital type I syndrome demonstrates an important role of this gene in human development.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Milan, Italy.
authors.forename: M I
authors.initials: MI
authors.lastname: Ferrante
authors.forename: G
authors.initials: G
authors.lastname: Giorgio
authors.forename: S A
authors.initials: SA
authors.lastname: Feather
authors.forename: A
authors.initials: A
authors.lastname: Bulfone
authors.forename: V
authors.initials: V
authors.lastname: Wright
authors.forename: M
authors.initials: M
authors.lastname: Ghiani
authors.forename: A
authors.initials: A
authors.lastname: Selicorni
authors.forename: L
authors.initials: L
authors.lastname: Gammaro
authors.forename: F
authors.initials: F
authors.lastname: Scolari
authors.forename: A S
authors.initials: AS
authors.lastname: Woolf
authors.forename: O
authors.initials: O
authors.lastname: Sylvie
authors.forename: L
authors.initials: L
authors.lastname: Bernard
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: R
authors.initials: R
authors.lastname: Winter
authors.forename: A
authors.initials: A
authors.lastname: Ballabio
authors.forename: B
authors.initials: B
authors.lastname: Franco
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D005091:Exons; D005145:Face / Q000002:abnormalities*; D005260:Female; D005385:Fingers / Q000002:abnormalities*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009056:Mouth Abnormalities / Q000235:genetics*; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D014034:Toes / Q000002:abnormalities*; D014960:X Chromosome
chemical_list: C115130:OFD1 protein, human; D011506:Proteins