Congenital neutropenia with retinopathy, a new phenotype without intellectual deficiency or obesity secondary to VPS13B mutations. Issue 2 (5th December 2013)

• Record Type: Journal Article
• Authors: Gueneau, Lucie; Duplomb, Laurence; Sarda, Pierre; Hamel, Christian; Aral, Bernard; Chehadeh, Salima El; Gigot, Nadège; St‐Onge, Judith; Callier, Patrick; Thevenon, Julien; Huet, Frédéric; Carmignac, Virginie; Droin, Nathalie; Faivre, Laurence; Thauvin‐Robinet, Christel
• Is Part Of: American journal of medical genetics. Volume 164:Issue 2(2014.)
• Page Start: 522
• Page End: 527
• Publication Date: 2013-12-05
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36300
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="ajmga36300-sec-0001" sec-type="section"> <p>Over one hundred <italic>VPS13B</italic> 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 <italic>VPS13B</italic> 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 <italic>VPS13B</italic> expression. RNA sequencing analysis up‐ and downstream from the IVS57+2T&gt;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 <italic>VPS13B</italic> analysis should be performed in cases of congenital neutropenia associated with retinopathy, even in the absence of ID, therefore extending the <italic>VPS13B</italic> phenotype spectrum. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>