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A novel mutation in the LIM homeobox 3 gene is responsible for combined pituitary hormone deficiency, hearing impairment, and vertebral malformations.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
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2009 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 4, 1154-1161 p.Article in journal (Refereed) Published
Abstract [en]

CONTEXT: The LIM homeobox 3 (LHX3) LIM-homeodomain transcription factor gene, found in both man and mouse, is required for development of the pituitary and motor neurons, and is also expressed in the auditory system. OBJECTIVE: The objective of this study was to determine the cause of, and further explore, the phenotype in six patients (aged 6 months to 22 yr) with combined pituitary hormone deficiency (CPHD), restricted neck rotation, scoliosis, and congenital hearing impairment. Three of the patients also have mild autistic-like behavior. DESIGN: Because patients with CPHD and restricted neck rotation have previously been shown to have mutations in the LHX3 gene, a candidate gene approach was applied, and the gene was sequenced. Neck anatomy was explored by computed tomography and magnetic resonance imaging, including three-dimensional reformatting. RESULTS: A novel, recessive, splice-acceptor site mutation was found. The predicted protein encoded by the mutated gene lacks the homeodomain and carboxyl terminus of the normal, functional protein. Genealogical studies revealed a common gene source for all six families dating back to the 17th century. Anatomical abnormalities in the occipito-atlantoaxial joints in combination with a basilar impression of the dens axis were found in all patients assessed. CONCLUSIONS: This study extends both the mutations known to be responsible for LHX3-associated syndromes and their possible phenotypical consequences. Previously reported traits include CPHD and restricted neck rotation; patients examined in the present study also show a severe hearing defect. In addition, the existence of cervical vertebral malformations are revealed, responsible for the rigid neck and the development of scoliosis.

Place, publisher, year, edition, pages
2009. Vol. 94, no 4, 1154-1161 p.
Keyword [en]
Hormone Deficiency, Hearing Impairment, Vertebral Malformations
National Category
Medical and Health Sciences
Research subject
URN: urn:nbn:se:umu:diva-34983DOI: 10.1210/jc.2008-0325PubMedID: 19126629OAI: diva2:327410
Available from: 2010-06-29 Created: 2010-06-29 Last updated: 2016-06-20Bibliographically approved

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Kriström, BeritZdunek, Anna-MaijaRydh, AndersJonsson, HåkanSehlin, PetraAndersson Escher, Stefan
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PaediatricsDiagnostic RadiologyOrthopaedicsOtorhinolaryngologyDepartment of Molecular Biology (Faculty of Medicine)
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