Congenital neutropenia with retinopathy, a new phenotype without intellectual deficiency or obesity secondary to VPS13B mutations

Lucie Gueneau, Laurence Duplomb, Pierre Sarda, Christian Hamel, Bernard Aral, Salima El Chehadeh, Nadège Gigot, Judith St-Onge, Patrick Callier, Julien Thevenon, Frédéric Huet, Virginie Carmignac, Nathalie Droin, Laurence Faivre, Christel Thauvin-Robinet

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    14 Citations (Scopus)

    Abstract

    Over one hundred VPS13B mutations are reported in Cohen syndrome (CS). Most cases exhibit a homogeneous phenotype that includes intellectual deficiency (ID), microcephaly, facial dysmorphism, slender extremities, truncal obesity, progressive chorioretinal dystrophy, and neutropenia. We report on a patient carrying two VPS13B splicing mutations with an atypical phenotype that included microcephaly, retinopathy, and congenital neutropenia, but neither obesity nor ID. RNA analysis of the IVS34+2T_+3AinsT mutation did not reveal any abnormal splice fragments but mRNA quantification showed a significant decrease in VPS13B expression. RNA sequencing analysis up- and downstream from the IVS57+2T>C mutation showed abnormal splice isoforms. In contrast to patients with typical CS, who express only abnormal VPS13B mRNA and truncated protein, a dose effect of residual normal VPS13B protein possibly explains the incomplete phenotype in the patient. This observation emphasizes that VPS13B analysis should be performed in cases of congenital neutropenia associated with retinopathy, even in the absence of ID, therefore extending the VPS13B phenotype spectrum.

    Original languageEnglish
    Pages (from-to)522-527
    Number of pages6
    JournalAmerican Journal of Medical Genetics, Part A
    Volume164
    Issue number2
    DOIs
    Publication statusPublished - 1 Feb 2014

    Keywords

    • Cohen syndrome
    • Dose effect
    • Splice mutations
    • VPS13B

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