Pierre Robin sequence may be caused by dysregulation of SOX9 and KCNJ2.
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.


CONCLUSIONS
Our findings suggest that non-syndromic PRS may be caused by both SOX9 and KCNJ2 dysregulation.
Jakobsen
Linda P
LP
Ullmann
Reinhard
R
Christensen
Steen B
SB
Jensen
Karl Erik
KE
Mølsted
Kirsten
K
Henriksen
Karen F
KF
Hansen
Claus
C
Knudsen
Mary A
MA
Larsen
Lars A
LA
Tommerup
Niels
N
Tümer
Zeynep
Z
D000293:Adolescent; D020029:Base Pairing / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D010855:Pierre Robin Syndrome / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014178:Translocation, Genetic
D006609:High Mobility Group Proteins; C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D014157:Transcription Factors