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Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy

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Abstract

Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.

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Acknowledgments

Funding for this study came from the Program on Neurogenetics at the Yale University School of Medicine (MG, MWS). We are greatly indebted to the patients for their participation in this study.

Financial disclosure

The authors report no competing financial interests.

Conflict of interest statement

The authors report no conflict of interest.

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Authors and Affiliations

  1. Department of Neurosurgery, Neurobiology, Program on Neurogenetics Yale University School of Medicine, New Haven, CT, USA

    Luis E. Kolb, Zulfikar Arlier, Ali K. Ozturk, Jennifer A. Moliterno, Fatih Bayrakli, Michael L. DiLuna, Katsuhito Yasuno, Kaya Bilguvar & Murat Gunel

  2. Department of Genetics, Program on Neurogenetics Yale University School of Medicine, New Haven, CT, USA

    Luis E. Kolb, Zulfikar Arlier, Ali K. Ozturk, Jennifer A. Moliterno, Fatih Bayrakli, Michael L. DiLuna, Katsuhito Yasuno, Kaya Bilguvar, Matthew W. State & Murat Gunel

  3. Division of Child Neurology, Department of Neurology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey

    Cengiz Yalcinkaya, Ozdem Erturk & Baris Korkmaz

  4. Department of Molecular Biology and Genetics, Faculty of Science and Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey

    Tayfun Ozcelik

  5. Division of Genetics, Department of Pediatrics, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey

    Beyhan Tuysuz

  6. Child Study Center and Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Matthew W. State

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  1. Luis E. Kolb
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Correspondence to Murat Gunel.

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Luis E. Kolb and Zulfikar Arlier contributed equally to this work.

Glossary of terms

SNP

Single nucleotide polymorphism

CNV

Copy number variation

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Kolb, L.E., Arlier, Z., Yalcinkaya, C. et al. Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy. Neurogenetics 11, 319–325 (2010). https://doi.org/10.1007/s10048-009-0232-y

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