title: Two novel variants in CNTNAP1 in two siblings presenting with congenital hypotonia and hypomyelinating neuropathy.
abstract: Homozygous frameshift variants in CNTNAP1 have recently been reported in patients with arthrogryposis and abnormal axon myelination. In two brothers with severe congenital hypotonia and foot deformities, we identified compound heterozygous variants in CNTNAP1, reporting the first causative missense variant, p.(Cys323Arg). Motor nerve conductions were markedly decreased. Nerve microscopical lesions confirmed a severe hypomyelinating process and showed loss of attachment sites of the myelin loops on the axons, which could be a characteristic of Caspr loss-of-function. We discuss the pathophysiology of the myelination process and we propose to consider this disorder as a congenital hypomyelinating neuropathy.
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Mathilde
authors: M
authors: Nizon
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Benjamin
authors: B
authors: Cogne
authors: Centre de référence « neuropathies périphériques rares », service de Neurologie, CHU Limoges, France.
authors: Jean-Michel
authors: JM
authors: Vallat
authors: Serviced' anatomopathologie, CHU Hôtel Dieu, Nantes, France.
authors: Madeleine
authors: M
authors: Joubert
authors: Service de réanimation pédiatrique, Hôpital Mère Enfants, Nantes, France.
authors: Jean-Michel
authors: JM
authors: Liet
authors: Service de réanimation néonatale, Hôpital Mère Enfants, Nantes, France.
authors: Laure
authors: L
authors: Simon
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Marie
authors: M
authors: Vincent
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Sébastien
authors: S
authors: Küry
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Pierre
authors: P
authors: Boisseau
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Sébastien
authors: S
authors: Schmitt
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Sandra
authors: S
authors: Mercier
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Claire
authors: C
authors: Bénéteau
authors: Pôle de biologie, Hôpital Mère Enfants, Nantes, France.
authors: Catherine
authors: C
authors: Larrose
authors: Pôle de biologie, Hôpital Mère Enfants, Nantes, France.
authors: Marianne
authors: M
authors: Coste
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Xénia
authors: X
authors: Latypova
authors: Service d'explorations fonctionnelles, CHU Hôtel Dieu, Nantes, France.
authors: Yann
authors: Y
authors: Péréon
authors: Serviced' anatomopathologie, CHU Hôtel Dieu, Nantes, France.
authors: Jean-Marie
authors: JM
authors: Mussini
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France.
authors: Stéphane
authors: S
authors: Bézieau
authors: Service de Génétique Médicale, CHU Hôtel Dieu, France. bertrand.isidor@chu-nantes.fr.
authors: Bertrand
authors: B
authors: Isidor
mesh_terms: D001176:Arthrogryposis / Q000235:genetics* / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D005530:Foot Deformities / Q000235:genetics* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D009186:Myelin Sheath / Q000235:genetics; D035781:Siblings
chemical_list: C491323:CNTNAP1 protein, human; D015816:Cell Adhesion Molecules, Neuronal