Elsevier

Brain and Development

Volume 31, Issue 6, June 2009, Pages 465-468
Brain and Development

Case report
A novel POMT2 mutation causes mild congenital muscular dystrophy with normal brain MRI

https://doi.org/10.1016/j.braindev.2008.08.005Get rights and content

Abstract

We report a patient harboring a novel homozygous mutation of c.604T > G (p.F202V) in POMT2. He showed delayed psychomotor development but acquired the ability to walk at the age of 3 years and 10 months. His brain MRI was normal. No ocular abnormalities were seen. Biopsied skeletal muscle revealed markedly decreased but still detectable glycosylated forms of alpha-dystroglycan (α-DG). Our results indicate that mutations in POMT2 can cause a wide spectrum of clinical phenotypes as observed in other genes associated with α-dystroglycanopathy. Presence of small amounts of partly glycosylated α-DG may have a role in reducing the clinical symptoms of α-dystroglycanopathy.

Introduction

Alpha-dystroglycan (α-DG) is a surface membrane protein that links extracellular basal lamina and intracellular cytoskeleton. α-DG is a highly glycosylated protein mainly composed of unique O-mannosyl glycans. Reduced/altered glycosylation of α-DG causes a wide variety of muscular dystrophies including Walker–Warburg syndrome (WWS), muscle-eye-brain disease (MEB), Fukuyama-type congenital muscular dystrophy (FCMD), congenital muscular dystrophies type 1C and type 1D, and limb girdle muscular dystrophies (LGMD) type 2I, 2K to 2N. They are collectively called alpha-dystroglycanopathies (α-DGP). So far, six causative genes for α-DGP have been identified including protein-O-mannosyl transferase 1 and 2 (POMT1 and POMT2), protein O-mannose β-1,2-N-acetylglucosaminyltransferase (POMGnT1), fukutin (FKTN), fukutin-related protein (FKRP), and acetylglucosaminyl transferase-like protein (LARGE). Here we report a mild congenital muscular dystrophy patient associated with a novel homozygous mutation in POMT2.

Section snippets

Case report

A 4-year-old Japanese boy, the only child from healthy consanguineous parents, was delivered uneventfully at full term. During few days after birth, he was low spirited and showed sucking weakness. Floppiness was not prominent but serum CK levels were markedly elevated up to 33,000 IU/l (normal < 70). His condition was improved within 2 weeks, but serum CK levels were persistently higher than 1000 IU/l. His motor milestones were delayed and he could control his head at 5 months of age. At

Discussion

POMT2 is the gene encoding an enzyme for protein O-mannosylation, and it is required to form a complex with POMT1 for the enzyme activity [2]. Recently, some patients with mutations in POMT2 have been reported [3], [4], [5], [6], [7], [8]. Most patients showed floppiness at birth, delayed psychomotor development, congenital muscular dystrophy, and severe mental retardation with or without ocular involvement. Brain anomalies are prominent including hydrocephalus, lissencephaly, agenesis of the

Acknowledgements

We thank Dr. S. Shalaby (National Institute of Neuroscience, NCNP) for reviewing the manuscript. K.P. Campbell is an investigator of the Howard Hughes Medical Institute. This study was supported by the Research on Health Sciences focusing on Drug Innovation from the Japanese Health Sciences Foundation, the Research on Psychiatric and Neurological Diseases and Mental Health of Health and Labor Sciences Research Grants, the Research Grant, for Nervous and Mental Disorders from the Ministry of

References (10)

There are more references available in the full text version of this article.

Cited by (9)

  • Uniparental disomy unveils a novel recessive mutation in POMT2

    2018, Neuromuscular Disorders
    Citation Excerpt :

    The majority of reported mutations in POMT2 are associated with severe congenital muscular dystrophy such as Walker–Warburg Syndrome [6]. Less frequently, POMT2 mutations lead to milder LGMD type 2N without brain or eye involvement except for mild intellectual disability [6,11–14]. In a recent series of 12 cases of LGMD2N [14], all twelve had cognitive impairment, two had decreased left ventricular ejection fraction, and the eight who were tested had decreased forced vital capacity.

  • A fourth case of POMT2-related limb girdle muscle dystrophy with mild reduction of α-dystroglycan glycosylation

    2014, European Journal of Paediatric Neurology
    Citation Excerpt :

    They are also heterogeneous at the genetic level: to date at least 18 causative genes have been identified in these disorders,2–14 and more are going to be found by the next generation sequencing techniques. Mutations in the POMT2 were first identified in patients with WWS and have been found also in patients with MEB-like phenotype or with milder LGMD features.15–22 The POMT2 gene encodes the protein O-mannosyltransferase 2 that forms a complex with O-mannosyltransferase 1 (POMT1) responsible for the catalysis of the first step in O-mannosyl glycan synthesis.23,24

View all citing articles on Scopus
View full text