Childhood onset homozygous recessive GDAP1 (p.Pro231Leu) mutation in a 9-year-old puerto rican pediatric female with axonal Charcot-Marie-Tooth disease: A case report

2021 ◽  
pp. 1-5
Author(s):  
Ana Ortiz-Santiago ◽  
Edwardo Ramos
Keyword(s):  
Puerto Rican ◽  
Mitochondrial Protein ◽  
Motor Neuropathy ◽  
Childhood Onset ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Old Order ◽  
Sensory Motor ◽  
History Of ◽  
Tooth Disease

Charcot-Marie-Tooth disease (CMT) is a progressive hereditary neuromuscular neuropathy with pathology in the myelin sheath or the axon. CMT caused by mutations in the Ganglioside-induced differentiation associated protein 1 (GDAP1) gene has been described by a spectrum of phenotypic presentations. GDAP1 is a mitochondrial protein responsible for protecting neuronal bodies from oxidative stress. It is associated with axonal and demyelinating pathophysiology with recessive and dominant modes of inheritance.We describe a case of a 9-year-old Puerto Rican female with clinical and electrodiagnostic results compatible with an axonal sensory-motor neuropathy where a genetic test describes a homozygous GDAP1 missense mutation at the c.692C>T (p.Pro231Leu), previously undetected in a pediatric Latino patient. Mutations in GDAP1 have been previously described in Tunisian, Old Order Amish, European and Japanese families with varying modes of inheritance. To our knowledge, this homozygous variant presentation of the GDAP1 gene is the first to be described in a pediatric Puerto Rican patient without a family history of hereditary sensory motor neuropathy.

scholarly journals Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a colombian family.

2015 ◽  
pp. 194-198 ◽  
Author(s):  
Angela Milena Martin ◽  
Silvia Juliana Maradei Anaya ◽  
Harvy Mauricio Velasco Parra
Keyword(s):  
Premature Stop Codon ◽  
Diaphragmatic Paralysis ◽  
Causative Mutation ◽  
Rehabilitation Service ◽  
Clinical Approach ◽  
South American ◽  
Motor Neuropathy ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Tooth Disease

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. Objective: We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. Methods: We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A. Results: The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.

scholarly journals Natural history of Charcot-Marie-Tooth disease during childhood

2017 ◽  
Vol 82 (3) ◽  
pp. 353-359 ◽  
Author(s):  
Kayla M.D. Cornett ◽  
Manoj P. Menezes ◽  
Rosemary R. Shy ◽  
Isabella Moroni ◽  
Emanuela Pagliano ◽  
...  
Keyword(s):  
Natural History ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
History Of ◽  
Tooth Disease

scholarly journals Noncompaction Cardiomyopathy with Charcot-Marie-Tooth Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Sherif Ali Eltawansy ◽  
Andrea Bakos ◽  
John Checton
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Genetic Disorders ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Noncompaction Cardiomyopathy ◽  
High Incidence ◽  
History Of ◽  
Tooth Disease ◽  
New Onset

We report a case of a 53-year-old female presenting with a new-onset heart failure that was contributed secondary to noncompaction cardiomyopathy. The diagnosis was made by echocardiogram and confirmed by cardiac MRI. Noncompaction cardiomyopathy (also known as ventricular hypertrabeculation) is a newly discovered disease. It is considered to be congenital (genetic) cardiomyopathy. It is usually associated with genetic disorders and that could explain the genetic pathogenesis of the non-compaction cardiomyopathy. Our case had a history of Charcot-Marie-Tooth disease. There is a high incidence of arrhythmia and embolic complications. The treatment usually consists of the medical management, defibrillator placement, and lifelong anticoagulation. Heart transplantation will be the last resort.

scholarly journals Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype

2021 ◽  
pp. jnnp-2021-327186
Author(s):  
Menelaos Pipis ◽  
Andrea Cortese ◽  
James M Polke ◽  
Roy Poh ◽  
Jana Vandrovcova ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Muscular Atrophy ◽  
Disease Type ◽  
Lower Limbs ◽  
Reading Frame ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
Neurophysiological Studies ◽  
History Of ◽  
Tooth Disease

ObjectiveNeurofilaments are the major scaffolding proteins for the neuronal cytoskeleton, and variants in NEFH have recently been described to cause axonal Charcot-Marie-Tooth disease type 2CC (CMT2CC).MethodsIn this large observational study, we present phenotype–genotype correlations on 30 affected and 3 asymptomatic mutation carriers from eight families.ResultsThe majority of patients presented in adulthood with motor-predominant and lower limb-predominant symptoms and the average age of onset was 31.0±15.1 years. A prominent feature was the development of proximal weakness early in the course of the disease. The disease progressed rapidly, unlike other Charcot-Marie-Tooth disease (CMT) subtypes, and half of the patients (53%) needed to use a wheelchair on average 24.1 years after symptom onset. Furthermore, 40% of patients had evidence of early ankle plantarflexion weakness, a feature which is observed in only a handful of CMT subtypes. Neurophysiological studies and MRI of the lower limbs confirmed the presence of a non-length-dependent neuropathy in the majority of patients.All families harboured heterozygous frameshift variants in the last exon of NEFH, resulting in a reading frameshift to an alternate open reading frame and the translation of approximately 42 additional amino acids from the 3' untranslated region (3′-UTR).ConclusionsThis phenotype–genotype study highlights the unusual phenotype of CMT2CC, which is more akin to spinal muscular atrophy rather than classic CMT. Furthermore, the study will enable more informative discussions on the natural history of the disease and will aid in NEFH variant interpretation in the context of the disease’s unique molecular genetics.

scholarly journals Clinical and genetic features of Charcot-Marie-Tooth disease 2F and hereditary motor neuropathy 2B in Japan

2018 ◽  
Vol 23 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Hajime Tanabe ◽  
Yujiro Higuchi ◽  
Jun-Hui Yuan ◽  
Akihiro Hashiguchi ◽  
Akiko Yoshimura ◽  
...  
Keyword(s):  
Motor Neuropathy ◽  
Charcot Marie Tooth ◽  
Hereditary Motor ◽  
Charcot Marie Tooth Disease ◽  
Hereditary Motor Neuropathy ◽  
Genetic Features ◽  
Tooth Disease
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