Neuropediatrics 2017; 48(S 01): S1-S45
DOI: 10.1055/s-0037-1602946
PP – Poster Presentations
Georg Thieme Verlag KG Stuttgart · New York

Remarkable Genetic Finding in a Girl with Phenotype of Classic Pelizäus-Merzbacher Disease: Xq22.2 Microdeletion Including PLP1 and Other Genes

Authors

  • C. Kehrer

    1   Department of Paediatric Neurology and Developmental Medicine, University Children’s Hospital, Tübingen, Germany

  • M. Kehrer

    2   Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany

  • S. Groeschel

    1   Department of Paediatric Neurology and Developmental Medicine, University Children’s Hospital, Tübingen, Germany

  • A. Dufke

    2   Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany

  • I. Krägeloh-Mann

    2   Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
Further Information

Publication History

Publication Date:
26 April 2017 (online)

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    Background: PLP1-related disorders are X-linked and include a range of clinical and neuro-radiological phenotypes from severe connatal and classic Pelizäus-Merzbacher disease (PMD), PLP1 null-syndrome to spastic paraplegia (SPG2). Most individuals with classic PMD have PLP1 duplications. Deletions of PLP1 are scarce. Female carriers may show mild neurological signs. Severely affected females with Xq22.2 microdeletions including PLP1 and skewed X-inactivation are reported; GLRA4, which in some cases also was deleted, is a novel candidate gene for X-linked intellectual disability.

    Methods: GJC2-gene analysis showed normal results. SNP microarray analysis and X inactivation study were performed. FISH was performed on the parents’ chromosomes. MRI was done at the age of 18 and 30 months and 11 years.

    Results: We report on a 14-year-old girl with features of classic PMD (developmental delay, infantile nystagmus, spasticity, intellectual disability, and behavioral disorder). Initial MRI was compatible with hypomyelination, but showed some progress in myelination of supratentorial white matter at the age of 11 years. SNP microarray showed an interstitial de novo deletion (651 kb) of Xq22.2 including PLP1 and GLRA4. X inactivation was randomized (60:40).

    Conclusion: Our patient with microdeletion Xq22.2 including the PLP1 gene showed clinical features of classic PMD, but some progress of myelination beyond what is defined as hypomyelination. Such a severely affected girl with randomized X-inactivation is not yet reported. Our case underlines a wide genotype–phenotype correlation. Deletion of neighboring genes including GLRA4, a novel candidate gene for X-linked intellectual disability, may play a role with regard to clinical severity.


     

    No conflict of interest has been declared by the author(s).