Inverted formin 2‐related Charcot‐Marie‐Tooth disease: extension of the mutational spectrum and pathological findings in Schwann cells and axons. Issue 1 (March 2015)

• Record Type: Journal Article
• Authors: Roos, Andreas; Weis, Joachim; Korinthenberg, Rudolf; Fehrenbach, Henry; Häusler, Martin; Züchner, Stephan; Mache, Christoph; Hubmann, Holger; Auer‐Grumbach, Michaela; Senderek, Jan
• Is Part Of: Journal of the peripheral nervous system. Volume 20:Issue 1(2015)
• Page Start: 52
• Page End: 59
• Publication Date: 2015-03
• Subjects: Nervous system -- Periodicals; Nerves, Peripheral -- Diseases -- Periodicals; Peripheral Nervous System Diseases -- Periodicals; Peripheral Nervous System -- Periodicals; 612.81
• DOI: 10.1111/jns.12106
• Languages: English
• ISSNs: 1085-9489

Abstract

<abstract abstract-type="main" id="jns12106-abs-0001"> <title> <bold>Abstract</bold> </title> <p id="jns12106-para-0001">Mutations in the gene encoding inverted formin FH2 and WH2 domain‐containing protein (INF2), a Cdc42 effector involved in the regulation of actin dynamics, cause focal segmental glomerulosclerosis (FSGS) and intermediate Charcot‐Marie‐Tooth neuropathy combined with FSGS (FSGS–CMT). Here, we report on six patients from four families with sensorimotor polyneuropathy and FSGS. Nerve conduction velocities were moderately slowed, and amplitudes of sensory and motor potentials were decreased. One patient had internal hydrocephalus and was intellectually disabled. Molecular genetic testing revealed two known and two novel missense mutations in the second and fourth exons of the <italic>INF2</italic> gene. Investigations of one nerve biopsy confirmed the diagnosis of intermediate‐type CMT and revealed occasional abnormal in‐ and outfoldings of myelin sheaths and expansions of the endoplasmic reticulum in axons and Schwann cells. While earlier reports suggested that mutations causing FSGS‐CMT are restricted to exons 2 and 3 of the <italic>INF2</italic> gene, we found one CMT‐FSGS causing mutation (p.Glu184Lys) in exon 4 extending the critical region of <italic>INF2</italic> for rapid CMT‐FSGS molecular genetic diagnosis. Study of a nerve biopsy showed abnormalities that might be related to the known role of the INF2‐binding partner CDC42 in myelination.</p> </abstract>