Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease

Julien Masliah-Planchon; Céline Dupont; George Vartzelis; Aurélien Trimouille; Eléonore Eymard-Pierre; Mathilde Gay-Bellile; Florence Renaldo; Imen Dorboz; Cécile Pagan; Samuel Quentin; Monique Elmaleh; Christina Kotsogianni; Elissavet Konstantelou; Séverine Drunat; Anne-Claude Tabet; Odile Boespflug-Tanguy

doi:10.1186/s12881-015-0226-6

Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease

Julien Masliah-Planchon ¹ Céline Dupont ² George Vartzelis ³ Aurélien Trimouille ¹ Eléonore Eymard-Pierre ^{4, 5} Mathilde Gay-Bellile ^{4, 5} Florence Renaldo ^{6, 1} Imen Dorboz ¹ Cécile Pagan ¹ Samuel Quentin ⁷ Monique Elmaleh ⁸ Christina Kotsogianni ³ Elissavet Konstantelou ³ Séverine Drunat ¹ Anne-Claude Tabet ² Odile Boespflug-Tanguy ^{1, 6, *}

* Auteur correspondant

1 PROTECT - Neuroprotection du Cerveau en Développement

2 UF de Cytogénétique

3 Paediatric Neurology

4 ERTICa - Equipe de recherche sur les traitements individualisés des cancers

5 Cytogénétique Médicale

6 Service de neurologie pédiatrique et maladies métaboliques

7 Institut Universitaire d'Hématologie

8 Service d'imagerie pédiatrique

Abstract : AbstractBackgroundPelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder characterized by nystagmus, hypotonia, ataxia, progressive spasticity, and cognitive decline. PMD classically results from a duplication of a genomic segment encompassing the entire PLP1 gene. Since the PLP1 gene is located in Xq22, PMD affects mostly boys.Methods and resultsHere we report the case of a girl with typical PMD. Copy number analysis of the PLP1 locus revealed a duplication of the entire gene and FISH analysis showed that the extra copy of the PLP1 gene was actually inserted in chromosome 1p36. This insertion of an additional copy of PLP1 in an autosome led to a functional duplication irrespective of the X-inactivation pattern. Subsequent overexpression of PLP1 was the cause of the PMD phenotype observed in this girl. Further sequencing of the breakpoint junction revealed a microhomology and thus suggested a replication based mechanism (such as FoSTeS or MMBIR).ConclusionThis case emphasizes the susceptibility of the PLP1 locus to complex rearrangement likely driven by the Xq22 local genomic architecture. In addition, careful consideration should be given to girls with classical PMD clinical features since they usually experience complex PLP1 genomic alteration with a distinct risk of inheritance.

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Article dans une revue

BMC Medical Genetics, BioMed Central, 2015, 16 (1), pp.77. 〈10.1186/s12881-015-0226-6〉

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Sciences du Vivant [q-bio]

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Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease

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Insertion of an extra copy of Xq22.2 into 1p36 results in functional duplication of the PLP1 gene in a girl with classical Pelizaeus-Merzbacher disease

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