[Holt-Oram syndrome: study of 7 cases].
FUNDAMENTAL AND OBJECTIVE: Holt-Oram syndrome (HOS) is a heart-hand disease with an autosomal dominant inheritance pattern. About 85% of the affected patients present de novo mutations in the TBX5 gene. The aim of this study is to propose a molecular strategy to diagnose patients with clinical suspicion of HOS.


METHODS
A sequence analysis of 7 patients from exon 2 to exon 8 of the TBX5 gene was performed. MLPAp179 and MLPAp180 were performed in those cases in which no mutation was found.


RESULTS
p.Arg270X and p.Ala34Glyfsx27 mutations were identified in 2 cases. These cases fulfilled the strict clinical criteria, had a family history of HOS and had similar clinical features. In other three cases, MLPA results showed deletions of the GLI3 coding region.


CONCLUSIONS
In order to increase the TBX5 mutation detection rate, an exhaustive physical examination focused on the strict clinical criteria may be necessary to rule out clinical overlapping syndromes. We propose that molecular analysis of GLI3 may be performed in patients with clinical suspicion of HOS without mutations in TBX5.
Servicio de Genética, Fundación Jiménez Díaz, Madrid, España. mmartinezg@fjd.es
Mónica
M
Martínez-García
Isabel
I
Lorda-Sanchez
Maria
M
García-Hoyos
Carmen
C
Ramos
Carmen
C
Ayuso
María José
MJ
Trujillo-Tiebas
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics; D000168:Acrocephalosyndactylia / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D018740:Genetic Heterogeneity; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics; D006344:Heart Septal Defects, Atrial / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D038061:Lower Extremity Deformities, Congenital / Q000175:diagnosis / Q000235:genetics; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D020825:T-Box Domain Proteins / Q000235:genetics*; D038062:Upper Extremity Deformities, Congenital / Q000175:diagnosis / Q000235:genetics; D000074290:Zinc Finger Protein Gli3
C065683:GLI3 protein, human; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D000074290:Zinc Finger Protein Gli3