Mutation in MEOX1 gene causes a recessive Klippel-Feil syndrome subtype

BMC Genetics

Hamit Zafer Kars¹  Unal Ozum¹  Burak Kazanci³  Ahmet Rasit Ozturk²  Sirin Yuksel⁵  Mahmut Samil Sagiroglu⁴  Bekir Erguner⁴  Ugur Kartal⁷  Hatice Balaban⁶  Cengiz Yakicier⁵  Bulent Guclu³  Fatih Bayrakli⁷ 

[1] Department of Neurosurgery, Cumhuriyet University School of Medicine, Kampus, Merkez, 58140, Sivas, Turkey;Informatics Institute, Middle East Technical University, Ankara, Turkey;Neurosurgery Clinic, Ministry of Health, Sevket Yilmaz Research and Training Hospital, Bursa, Turkey;TUBITAK BILGEM, Kocaeli, Turkey;Department of Medical Biology, Acibadem University School of Medicine, İstanbul, Turkey;Department of Neurology, Cumhuriyet University School of Medicine, Sivas, Turkey;Molecular Neurogenetics Research Laboratory, Department of Neurosurgery, Cumhuriyet University School of Medicine, Sivas, Turkey

关键词: Whole genome linkage analysis;    Vertebra;    Whole-exome sequencing;    MEOX1;    Klippel-Feil syndrome;   

Others  :  1086577
DOI  :  10.1186/1471-2156-14-95

 received in 2013-06-19, accepted in 2013-09-26,  发布年份 2013

【 摘 要 】

Background

Klippel-Feil syndrome (KFS) is characterized by the developmental failure of the cervical spine and has two dominantly inherited subtypes. Affected individuals who are the children of a consanguineous marriage are extremely rare in the medical literature, but the gene responsible for this recessive trait subtype of KFS has recently been reported.

Results

We identified a family with the KFS phenotype in which their parents have a consanguineous marriage. Radiological examinations revealed that they carry fusion defects and numerical abnormalities in the cervical spine, scoliosis, malformations of the cranial base, and Sprengel’s deformity. We applied whole genome linkage and whole-exome sequencing analysis to identify the chromosomal locus and gene mutated in this family. Whole genome linkage analysis revealed a significant linkage to chromosome 17q12-q33 with a LOD score of 4.2. Exome sequencing identified the G > A p.Q84X mutation in the MEOX1 gene, which is segregated based on pedigree status. Homozygous MEOX1 mutations have reportedly caused a similar phenotype in knockout mice.

Conclusions

Here, we report a truncating mutation in the MEOX1 gene in a KFS family with an autosomal recessive trait. Together with another recently reported study and the knockout mouse model, our results suggest that mutations in MEOX1 cause a recessive KFS phenotype in humans.

【 授权许可】

   
2013 Bayrakli et al.; licensee BioMed Central Ltd.

【 图 表 】

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