1. Mutation in MEOX1 gene causes a recessive Klippel-Feil syndrome subtype
- Author
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Fatih Bayrakli, Bulent Guclu, Ünal Özüm, Burak Kazanci, Ahmet Rasit Ozturk, Cengiz Yakicier, Hamit Zafer Kars, Mahmut Şamil Sağıroğlu, Şirin Yüksel, Hatice Balaban, Ugur Kartal, Bekir Ergüner, Acibadem University Dspace, and [Bayrakli, Fatih -- Ozum, Unal -- Kars, Hamit Zafer] Cumhuriyet Univ, Sch Med, Dept Neurosurg, TR-58140 Merkez, Sivas, Turkey -- [Bayrakli, Fatih -- Kartal, Ugur] Cumhuriyet Univ, Sch Med, Dept Neurosurg, Mol Neurogenet Res Lab, Sivas, Turkey -- [Guclu, Bulent -- Kazanci, Burak] Sevket Yilmaz Res & Training Hosp, Minist Hlth, Neurosurg Clin, Bursa, Turkey -- [Yakicier, Cengiz -- Yuksel, Sirin] Acibadem Univ, Sch Med, Dept Med Biol, Istanbul, Turkey -- [Balaban, Hatice] Cumhuriyet Univ, Sch Med, Dept Neurol, Sivas, Turkey -- [Erguner, Bekir -- Sagiroglu, Mahmut Samil] TUBITAK BILGEM, Kocaeli, Turkey -- [Ozturk, Ahmet Rasit] Middle E Tech Univ, Inst Informat, TR-06531 Ankara, Turkey
- Subjects
Adult ,Male ,Genetic Linkage ,Klippel–Feil syndrome ,Locus (genetics) ,Klippel-Feil syndrome ,Biology ,medicine.disease_cause ,Bioinformatics ,Polymorphism, Single Nucleotide ,Whole genome linkage analysis ,Autosomal recessive trait ,Mice ,Genetic linkage ,Genetics ,medicine ,Animals ,Humans ,Genetics(clinical) ,Gene ,Genetics (clinical) ,Exome sequencing ,Vertebra ,Homeodomain Proteins ,Mutation ,Genome, Human ,Homozygote ,High-Throughput Nucleotide Sequencing ,medicine.disease ,MEOX1 ,Spine ,Pedigree ,Phenotype ,Whole-exome sequencing ,Female ,Lod Score ,Tomography, X-Ray Computed ,Consanguineous Marriage ,Research Article ,Chromosomes, Human, Pair 17 ,Transcription Factors - Abstract
WOS: 000325205700001, PubMed ID: 24073994, 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., Cumhuriyet University [T-455, T-496], This work is supported by the Scientific Research Project Fund of Cumhuriyet University under project numbers T-455 and T-496.
- Published
- 2013