Mutation in IFT80 in a fetus with the phenotype of Verma-Naumoff provides molecular evidence for Jeune-Verma-Naumoff dysplasia spectrum.
BACKGROUND
The lethal group of short-rib polydactyly (SRP) includes type I (Saldino-Noonan; MIM 263530), type II (Majewski; MIM 263520), type III (Verma-Naumoff; MIM 263510) and type IV (Beemer-Langer; MIM 269860). Jeune and Ellis-van Creveld dysplasias also used to be classified in the SRP group. Recently, mutations in a gene encoding a protein involved in intraflagellar transport, IFT80, have been identified in 3/39 patients with Jeune dysplasia but no extraskeletal manifestation.


METHODS
Because of clinical and radiological similarities between Jeune dysplasia and the other lethal types of SRP, the authors decided to investigate IFT80 in a cohort of fetuses with the lethal forms of SRP (Majewski, Verma-Naumoff and Beemer-Langer) and antenatally diagnosed cases of Jeune dysplasia. Fifteen fetuses were identified. A double-molecular approach was adopted. For consanguineous families and for those with recurrent sibs, a haplotype analysis around the gene locus was first performed, and, for the others, all the coding exons of IFT80 were directly sequenced.


RESULTS
Using the haplotype approach for two families, the authors excluded the IFT80 region as a candidate for them. Direct sequencing of IFT80 in the other 13 cases showed a G-to-C transversion in exon 8 (G241R) in only one SRP case closely related to the type III phenotype.


CONCLUSIONS
The findings show that mutations in IFT80 can also be responsible for a lethal form of SRP and provide the molecular basis for the Jeune-Verma-Naumoff dysplasia spectrum.
Cavalcanti
Denise P
DP
Perinatal Genetic Program, Department of Medical Genetic, FCM, UNICAMP, Campinas, São Paulo, Brazil. denisepc@unicamp.br
Huber
Celine
C
Sang
Kim-Hanh Le Quan
KH
Baujat
Geneviève
G
Collins
Felicity
F
Delezoide
Anne-Lise
AL
Dagoneau
Nathalie
N
Le Merrer
Martine
M
Martinovic
Jelena
J
Mello
Marcos Fernando S
MF
Vekemans
Michel
M
Munnich
Arnold
A
Cormier-Daire
Valerie
V
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004613:Ellis-Van Creveld Syndrome / Q000235:genetics / Q000473:pathology; D005333:Fetus; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D012779:Short Rib-Polydactyly Syndrome / Q000235:genetics / Q000473:pathology
D002352:Carrier Proteins; D005819:Genetic Markers; C530863:IFT80 protein, human