TY - JOUR
T1 - Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2
AU - Jakobsen, Linda P
AU - Ullmann, Reinhard
AU - Christensen, Steen B
AU - Jensen, Karl Erik
AU - Mølsted, Kirsten
AU - Henriksen, Karen F
AU - Hansen, Claus
AU - Knudsen, Mary A
AU - Larsen, Lars A
AU - Tommerup, Niels
AU - Tümer, Zeynep
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
KW - Adolescent
KW - Base Pairing/genetics
KW - Child
KW - Child, Preschool
KW - Chromosome Breakage
KW - Chromosomes, Human, Pair 17/genetics
KW - Chromosomes, Human, Pair 2/genetics
KW - Female
KW - Gene Expression Regulation
KW - High Mobility Group Proteins/genetics
KW - Humans
KW - In Situ Hybridization, Fluorescence
KW - Lymphocytes/metabolism
KW - Male
KW - Pierre Robin Syndrome/genetics
KW - Potassium Channels, Inwardly Rectifying/genetics
KW - RNA, Messenger/genetics
KW - SOX9 Transcription Factor
KW - Transcription Factors/genetics
KW - Translocation, Genetic
U2 - 10.1136/jmg.2006.046177
DO - 10.1136/jmg.2006.046177
M3 - Journal article
C2 - 17551083
SN - 0022-2593
VL - 44
SP - 381
EP - 386
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 6
ER -