Dystrophinopathy in a Family Due to a Rare Nonsense Mutation Causing Predominant Behavioral Phenotype

Yohei Harada; Seth T. Sorensen; Akilandeswari Aravindhan; Vikki Stefans; Aravindhan Veerapandiyan

doi:10.1055/s-0039-1698437

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2020; 18(04): 210-213
DOI: 10.1055/s-0039-1698437

Case Report

Georg Thieme Verlag KG Stuttgart · New York

Dystrophinopathy in a Family Due to a Rare Nonsense Mutation Causing Predominant Behavioral Phenotype

Yohei Harada‡^*

¹Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

,

Seth T. Sorensen‡^*

²Division of Psychology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

,

Akilandeswari Aravindhan

³Division of Neurology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

,

Vikki Stefans

⁴Departments of Pediatrics and Physical Medicine and Rehabilitation, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

,

Aravindhan Veerapandiyan

³Division of Neurology, Department of Pediatrics, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States

› Author Affiliations

Abstract

Dystrophinopathies are a group of X-linked neuromuscular disorders resulting from mutations in DMD gene that encodes dystrophin. The clinical spectrum includes Duchenne muscular dystrophy, Becker muscular dystrophy, X-linked cardiomyopathy, and intellectual disability without involvement of skeletal muscle. Cognitive and behavioral problems are commonly seen among patients with dystrophinopathy. DMD gene is the largest human gene, consisting of 79 exons that produce dystrophin protein. Patients with genetic changes involving shorter dystrophin isoforms such as Dp140 and Dp71 are suggested to have higher rates of intellectual disability, attention-deficit/hyperactivity disorder, and other neuropsychiatric comorbidities. We describe three brothers who presented with prominent neurobehavioral deficits of varying degree, mild proximal weakness, and elevated serum creatine kinase due to a rare nonsense mutation, c.1702C > T; p.Gln568X, in exon 14 of DMD gene. Further studies are needed to better understand the effects of this rare mutation.

Keywords

DMD - Duchenne - Becker - mutation - muscular dystrophy

Full Text

References

References
1 Darras BT, Urion DK, Ghosh PS. Dystrophinopathies. In: Adam MP, Ardinger HH, Pagon RA. , et al, eds. GeneReviews (R). Seattle (WA): University of Washington; 1993
2 Traverso M, Assereto S, Baratto S. , et al. Clinical and molecular consequences of exon 78 deletion in DMD gene. J Hum Genet 2018; 63 (06) 761-764
3 Khadilkar Sv, Patil SG, Dastur RS, Gaitonde PS, Nadkarni JJ. 30. Duchenne muscular dystrophy: study of double deletions and familial cases. J Pediatr Neurol 2006; 4: 75-82
4 Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol 2003; 2 (12) 731-740
5 Moizard MP, Billard C, Toutain A, Berret F, Marmin N, Moraine C. Are Dp71 and Dp140 brain dystrophin isoforms related to cognitive impairment in Duchenne muscular dystrophy?. Am J Med Genet 1998; 80 (01) 32-41
6 Taylor PJ, Betts GA, Maroulis S. , et al. Dystrophin gene mutation location and the risk of cognitive impairment in Duchenne muscular dystrophy. PLoS One 2010; 5 (01) e8803
7 Cyrulnik SE, Fee RJ, De Vivo DC, Goldstein E, Hinton VJ. Delayed developmental language milestones in children with Duchenne's muscular dystrophy. J Pediatr 2007; 150 (05) 474-478
8 Hendriksen JG, Vles JS. Neuropsychiatric disorders in males with Duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive--compulsive disorder. J Child Neurol 2008; 23 (05) 477-481
9 Pane M, Lombardo ME, Alfieri P. , et al. Attention deficit hyperactivity disorder and cognitive function in Duchenne muscular dystrophy: phenotype-genotype correlation. J Pediatr 2012; 161 (04) 705-9.e1
10 Banihani R, Smile S, Yoon G. , et al. Cognitive and neurobehavioral profile in boys with Duchenne muscular dystrophy. J Child Neurol 2015; 30 (11) 1472-1482
11 Hinton VJ, Nereo NE, Fee RJ, Cyrulnik SE. Social behavior problems in boys with Duchenne muscular dystrophy. J Dev Behav Pediatr 2006; 27 (06) 470-476
12 Ricotti V, Mandy WP, Scoto M. , et al. Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations. Dev Med Child Neurol 2016; 58 (01) 77-84
13 Hinton VJ, Cyrulnik SE, Fee RJ. , et al. Association of autistic spectrum disorders with dystrophinopathies. Pediatr Neurol 2009; 41 (05) 339-346
14 Cotton S, Voudouris NJ, Greenwood KM. Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Dev Med Child Neurol 2001; 43 (07) 497-501
15 Felisari G, Martinelli Boneschi F, Bardoni A. , et al. Loss of Dp140 dystrophin isoform and intellectual impairment in Duchenne dystrophy. Neurology 2000; 55 (04) 559-564