Journal of medical genetics · 2007
Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2.
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Jakobsen Linda P, Ullmann Reinhard, Christensen Steen B, Jensen Karl Erik, Mølsted Kirsten, Henriksen Karen F, Hansen Claus, Knudsen Mary A, Larsen Lars A, Tommerup Niels, Tümer Zeynep
Аннотация
BACKGROUND: The Pierre Robin sequence (PRS), consisting of cleft palate, micrognathia and glossoptosis, can be seen as part of the phenotype in other Mendelian syndromes--for instance, campomelic dysplasia (CD) which is caused by SOX9 mutations--but the aetiology of non-syndromic PRS has not yet been unravelled.
OBJECTIVE: To gain more insight into the aetiology of PRS by studying patients with PRS using genetic and cytogenetic methods.
METHODS: 10 unrelated patients with PRS were investigated by chromosome analyses and bacterial artificial chromosome arrays. A balanced translocation was found in one patient, and the breakpoints were mapped with fluorescence in situ hybridisation and Southern blot analysis. All patients were screened for SOX9 and KCNJ2 mutations, and in five of the patients expression analysis of SOX9 and KCNJ2 was carried out by quantitative real-time PCR.
RESULTS: An abnormal balanced karyotype 46,XX, t(2;17)(q23.3;q24.3) was identified in one patient with PRS and the 17q breakpoint was mapped to 1.13 Mb upstream of the transcription factor SOX9 and 800 kb downstream of the gene KCNJ2. Furthermore, a significantly reduced SOX9 and KCNJ2 mRNA expression was observed in patients with PRS.
CONCLUSION: Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.
OBJECTIVE: To gain more insight into the aetiology of PRS by studying patients with PRS using genetic and cytogenetic methods.
METHODS: 10 unrelated patients with PRS were investigated by chromosome analyses and bacterial artificial chromosome arrays. A balanced translocation was found in one patient, and the breakpoints were mapped with fluorescence in situ hybridisation and Southern blot analysis. All patients were screened for SOX9 and KCNJ2 mutations, and in five of the patients expression analysis of SOX9 and KCNJ2 was carried out by quantitative real-time PCR.
RESULTS: An abnormal balanced karyotype 46,XX, t(2;17)(q23.3;q24.3) was identified in one patient with PRS and the 17q breakpoint was mapped to 1.13 Mb upstream of the transcription factor SOX9 and 800 kb downstream of the gene KCNJ2. Furthermore, a significantly reduced SOX9 and KCNJ2 mRNA expression was observed in patients with PRS.
CONCLUSION: Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.
Предметные рубрики MeSH
AdolescentBase PairingChildChild, PreschoolChromosome BreakageChromosomes, Human, Pair 17Chromosomes, Human, Pair 2FemaleGene Expression RegulationHigh Mobility Group ProteinsHumansIn Situ Hybridization, FluorescenceLymphocytesMalePierre Robin SyndromePotassium Channels, Inwardly RectifyingRNA, MessengerSOX9 Transcription FactorTranscription FactorsTranslocation, Genetic