3110

MNX1

HB9|HLXB9|HOXHB9|SCRA1;motor neuron and pancreas homeobox 1;MNX1;motor neuron and pancreas homeobox 1

homeobox HB9|homeobox protein HB9|motor neuron and pancreas homeobox protein 1

7q36

protein-coding

BACKGROUND: The HLXB9 gene encodes a homeodomain containing transcription factorwhich has been implicated in the development of both solid and hematological malignancies. In leukemia it is one of the two fused genes, along with ETV6, in a recurrent translocation frequently observed in infant AML. PROCEDURE: Here we investigate the role of epigenetic inactivation of the HLXB9 gene in leukemia. Quantitative DNA methylation analysis was performed using the COBRA assay, and qRT-PCR was used to assess the effects of methylation on expression in hematological cell lines and primary ALL samples. RESULTS: Hypermethylation of the HLXB9 gene was found to be a frequent event in childhood ALL, occurring in 33% of cases. However, it was rarely or never observed in other types of leukemia, including AML, CML, and CLL, with the exception of adult ALL, in which39% of cases were hypermethylated. Furthermore, hypermethylation of HLXB9 results in loss of expression in hematological cell lines and primary ALL samples. CONCLUSION: These results suggest that HLXB9 may have a dual role in childhood leukemia, as an oncogene in infant AML but as a tumor suppressor in childhood ALL.#CI- (c) 2010 Wiley-Liss, Inc.

OBJECTIVE: Currarino syndrome (CS) comprises a presacral mass, anorectal malformation, and a sacral bony defect. It is rarely reported in the gynecological field. CASE REPORT: We describe here the case of a 26-year-old married woman with Currarino syndrome who presented with a presacral teratoma and a previously unreported insertion in MNX1 gene. She had had a pelvic teratoma diagnosed by laparoscopy 8 years previously. She was referred to our clinic because of the increasing size of the teratoma and associated compression symptoms. Computed tomography demonstrated a heterogeneous 12 cm mass in the presacral region. Spina bifida at S2eS5 was also noted. Laparotomy confirmed thediagnosis of presacral teratoma. Genetic analysis disclosed a triple CGC repeat insertion in exon 1 of MNX1, resulting in three in-frame shifts encoding for theamino acid alanine. No siblings had known similar symptoms. CONCLUSION: Currarino syndrome is known to be an autosomal dominant disorder. The presence of constipation can lead to a diagnosis of the syndrome early in childhood. In sporadic cases diagnosis is late because of atypical symptoms. Delayed treatmentof a presacral tumor may cause serious complications such as central nervous system infection or subsequent neurological dysfunction. In clinical practice, apresacral tumor with a sacral bony defect may indicate Currarino syndrome. Genetic analysis of the family may provide information on the hereditary traits of specific MNX1 mutation.#CI- Copyright (c) 2011. Published by Elsevier B.V.