Recessive Charcot-Marie-Tooth and multiple sclerosis associated with a variant in MCM3AP

Maryam Sedghi; Ali-Reza Moslemi; Macarena Cabrera-Serrano; Behnaz Ansari; Majid Ghasemi; Mojtaba Baktashian; Ali Fattahpour; Homa Tajsharghi

doi:10.1093/braincomms/fcz011

Recessive Charcot-Marie-Tooth and multiple sclerosis associated with a variant in MCM3AP

Brain Commun. 2019 Sep 3;1(1):fcz011. doi: 10.1093/braincomms/fcz011. eCollection 2019.

Authors

Maryam Sedghi¹, Ali-Reza Moslemi², Macarena Cabrera-Serrano^{3

4}, Behnaz Ansari⁵, Majid Ghasemi⁵, Mojtaba Baktashian¹, Ali Fattahpour⁶, Homa Tajsharghi⁷

Affiliations

¹ Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
² Department of Pathology, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
³ Department of Neurology, Hospital Universitario Virgen del Rocio, Sevilla, Spain.
⁴ Instituto de Biomedicina de Sevilla, Universidad de Sevilla, Sevilla, Spain.
⁵ Department of neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
⁶ Radiology Resident, Department of Radiology, Mashhad University of Medical Sciences, Mashhad, Iran.
⁷ Division of Biomedicine, School of Health Science, University of Skovde, SE-541 28 Skovde, Sweden.

Abstract

Variants in MCM3AP, encoding the germinal-centre associated nuclear protein, have been associated with progressive polyneuropathy with or without intellectual disability and ptosis in some cases, and with a complex phenotype with immunodeficiency, skin changes and myelodysplasia. MCM3AP encoded protein functions as an acetyltransferase that acetylates the replication protein, MCM3, and plays a key role in the regulation of DNA replication. In this study, we report a novel variant in MCM3AP (p.Ile954Thr), in a family including three affected individuals with characteristic features of Charcot-Marie-Tooth neuropathy and multiple sclerosis, an inflammatory condition of the central nervous system without known genetic cause. The affected individuals were homozygous for a missense MCM3AP variant, located at the Sac3 domain, which was predicted to affect conserved amino acid likely important for the function of the germinal-centre associated nuclear protein. Our data support further expansion of the clinical spectrum linked to MCM3AP variant and highlight that MCM3AP should be considered in patients with accompaniment of recessive motor axonal Charcot-Marie-Tooth neuropathy and multiple sclerosis.

Keywords: Charcot-Marie-Tooth; GANP; MCM3AP; multiple sclerosis; neuropathy.