scholarly journals New mutation in the TRIP4 gene associated with congenital muscular dystrophy Davignon–Chauveau type (clinical case)

2021 ◽  
Vol 11 (3) ◽  
pp. 51-63
Author(s):  
T. V. Kozhanova ◽  
S. S. Zhilina ◽  
T. I. Mescheryakova ◽  
M. Yu. Shorina ◽  
I. F. Demenshin ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Clinical Case ◽  
Congenital Muscular Dystrophy ◽  
Neuromuscular Diseases ◽  
Homozygous Mutation ◽  
Rare Form ◽  
Progressive Muscle Weakness ◽  
Whole Exome ◽  
Heterozygous Variant ◽  
First Time

Congenital muscular dystrophies are heterogeneous groups of neuromuscular diseases leading to hypotonia, progressive muscle weakness and dystrophic or structural signs in muscle biopsy. At the present time, 34 genes associated with congenital muscular dystrophy have been described. The clinical case of a rare form of congenital muscular dystrophia associated with a homozygous mutation in the TRIP4 gene in a patient with respiratory failure requiring respiratory support, neurological symptoms, muscular hypotonia, and multiple congenital malformations of skeletal system is presented for the first time in Russia. The undescribed pathogenic homozygous variant of the nucleotide sequence in the TRIP4 gene (chr15:64686179, c.136C>T, p.Arg46Ter, 2 exon, NM_016213.4) was detected by whole exome sequencing. The mutation in the TRIP4 gene was validated by Sanger sequencing in a child and its origin was investigated. The mother and father of the girl are carriers of the heterozygous variant in the TRIP4 gene. Identification of the genetic cause of a rare form of neuromuscular disease is important for determining the tactics of patient management and medical and genetic counseling of the family, as well as clarifying the pathogenesis of a rare pathology. 

scholarly journals Clinical and genetic characteristics of congenital muscular dystrophies (Part 1)

2020 ◽  
Vol 10 (1) ◽  
pp. 10-21 ◽  
Author(s):  
P. A. Chausova ◽  
O. P. Ryzhkova ◽  
A. V. Polyakov
Keyword(s):  
Muscular Dystrophy ◽  
Clinical Symptoms ◽  
Muscle Protein ◽  
Molecular Genetic ◽  
Laboratory Data ◽  
Congenital Muscular Dystrophy ◽  
Neuromuscular Diseases ◽  
Muscular Hypotonia ◽  
Genetic Characteristics ◽  
Progressive Muscle Weakness

Congenital muscular dystrophy is an extremely heterogeneous group of hereditary neuromuscular diseases that are clinically characterized by muscular hypotonia, progressive muscle weakness, and dystrophic changes in the muscles. Overlapping clinical symptoms and many genes that have to be analyzed to determine the specific form of the disease in the patient make diagnosis difficult. The molecular genetic stage of diagnosis includes many different methods depending on the clinical hypothesis and their application has not lost its relevance even in the era of massive parallel sequencing. In addition to DNA sequence analysis, the analysis of muscle protein expression can also play a significant role in the diagnosis of congenital muscular dystrophy. In the review, we will consider the most important etiological, pathophysiological, clinical and laboratory data of the main forms of congenital muscular dystrophy known today.

Identification of two novel variants in GAA underlying infantile-onset Pompe disease in two Pakistani families

2020 ◽  
Vol 33 (4) ◽  
pp. 553-556
Author(s):  
Aman Ullah ◽  
Bibi Zubaida ◽  
Huma Arshad Cheema ◽  
Muhammad Naeem
Keyword(s):  
Pompe Disease ◽  
Age Of Onset ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Sequence Variations ◽  
Heterozygous Variant ◽  
Novel Variants ◽  
Carrier Identification ◽  
First Time ◽  
Pakistani Families

AbstractBackgroundPompe disease (PD) is an autosomal recessive metabolic myopathy with an average incidence of one in 40,000 live births. It has a variable age of onset and can be diagnosed within the first 3 months. Heart involvement and muscle weakness are its primary manifestations.Case presentationWe describe two families affected by PD with two rare, novel variants. To date, pathogenic variants in acid α-glucosidase (GAA) alone have accounted for all cases of the disease. Both families were screened for pathogenic sequence variations. This study presents the implications of regulatory or modifier sequences in the disease pathogenesis for the first time. A homozygous missense p.Arg854Gln variant in family A and a single heterozygous variant (p.Asn925His) in family B were found to be segregating according to the disease phenotype. The variants were not detected in our in-house database comprising 50 whole-exome sequences of healthy individuals from a local unrelated Pakistani population. In silico analyses predicted that the variants would have deleterious effects on the protein structure.ConclusionsThe variants likely underlie the infantile-onset PD (IOPD) in these Pakistani families. The study expands the mutation spectrum of GAA associated with IOPD and highlights the insufficiency of screening the GAA coding sequence to determine the cause of IOPD. The work should be helpful in carrier identification, improving genetic counselling, and prenatal diagnosis.

CNS findings in congenital muscular dystrophy 1A (with laminin alpha-2-deficiency)

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Cornelia Köhler ◽  
Katharina Weigt-Usinger ◽  
Christoph Heyer ◽  
Charlotte Thiels ◽  
Gabriele Dekomien ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Grey Matter ◽  
Pediatric Patients ◽  
Congenital Muscular Dystrophy ◽  
White Matter Lesions ◽  
Muscular Hypotonia ◽  
Mri Findings ◽  
Mri Scan ◽  
Progressive Muscle Weakness ◽  
The Brain

AbstractCongenital muscular dystrophy (MDC) is a group of rare hereditary myopathies with an early onset of progressive muscle weakness and dystrophic changes as evidenced by muscle biopsy. Some forms are associated with severe malformations of the brain. This study presented 2 pediatric patients with genetically diagnosed congenital muscular dystrophy 1A. The patients exhibited a typical combination of muscular hypotonia, joint contractures and elevated creatine kinase levels. Characteristic white matter lesions were not present in an early MRI scan of one patient, but could be detected at the age of 18 months. The second patient showed both severe white and grey matter abnormalities (pachy microgyria) in the MRI scan. In both cases, MRI findings did not correlate with the mental development of the patients.

Mutations in LAMA2 and CAPN3 genes associated with genetic and phenotypic heterogeneities within a single consanguineous family involving both congenital and progressive muscular dystrophies

2010 ◽  
Vol 31 (2) ◽  
pp. 125-135 ◽  
Author(s):  
Ikhlass Hadj Salem ◽  
Fatma Kamoun ◽  
Nacim Louhichi ◽  
Souad Rouis ◽  
Mariam Mziou ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Age Of Onset ◽  
Neuromuscular Disorders ◽  
Congenital Muscular Dystrophy ◽  
Premature Termination Codon ◽  
The Other ◽  
Homozygous Mutation ◽  
Reverse Transcription Pcr ◽  
Frameshift Deletion ◽  
Nonsense Mediated Mrna Decay

LGMD (limb-girdle muscular dystrophy) and CMD (congenital muscular dystrophy) are two common forms of neuromuscular disorders which are distinguishable by their age of onset but with probably a similar underlying pathway. In the present study, we report immunohistochemical, Western-blot and genetic analyses in a large consanguineous Tunisian family with two branches, including seven patients sharing similar LGMD2 phenotype in one branch and one CMD patient in the other branch. Linkage analyses were compatible with the LGMD2A locus in one branch and the MDC1A (muscular dystrophy congenital type 1A) locus in the other branch. This result was supported by deficiency in merosin and calpain3 in the CMD patient and LGMD patients respectively. Mutation analysis revealed two distinct mutations: a c.8005delT frameshift deletion in exon 56 of the LAMA2 (laminin-α2) gene (MDC1A) was found in the CMD patient and a new homozygous mutation c.1536+1G>T in the donor splice site of intron 12 of the CAPN3 (calpain3) gene (LGMD2A) was found in the LGMD patients. RT–PCR (reverse transcription–PCR) performed on total RNA from a LGMD2A patient's muscle biopsy showed complete retention of intron 12 in CAPN3 cDNA, generating a PTC (premature termination codon) that potentially elicits degradation of the nonsense mRNA by NMD (nonsense-mediated mRNA decay). Our results indicate that mRNA analysis is necessary to clarify the primary effect of genomic mutations on splicing efficiency that alters mRNA processing and expression level.

A difficult path to the diagnosis of hereditary polysystemic diseases as an example of a clinical case

2020 ◽  
pp. 68-70
Author(s):  
Ю.В. Максимова ◽  
М.А. Васильева ◽  
В.Н. Максимов
Keyword(s):  
Muscular Dystrophy ◽  
Training Program ◽  
Marfan Syndrome ◽  
Clinical Case ◽  
Fatal Outcome ◽  
Neuromuscular Diseases ◽  
Late Diagnosis ◽  
Hereditary Diseases ◽  
Increased Risk ◽  
Pleiotropic Action

Наследственные заболевания часто бывают полисистемными вследствие плейотропного действия генов. Примеров можно привести много: болезнь Вильсона-Коновалова, синдром Марфана, многие нервно-мышечные заболевания. Одно из таких заболеваний - мышечная дистрофия Эмери-Дрейфуса (МДЭД). Описан клинический случай, когда диагноз был поставлен юноше только в 18 лет. Недостаточная осведомлённость врачей о наследственных заболеваниях с повышенным риском развития внезапной сердечной смерти приводит к их запоздалой диагностике или фатальному исходу на фоне высоких нагрузок какие часто бывают у спортсменов, военнослужащих срочной службы. Hereditary diseases are often polysystemic due to the pleiotropic action of genes. There are many examples: Wilson-Konovalov disease, Marfan syndrome, many neuromuscular diseases. One of these diseases is Emery-Dreyfus muscular dystrophy (DMED). A clinical case is described when the boy was diagnosed only at the age of 18. The lack of awareness of doctors about hereditary diseases with an increased risk of SCD leads to their extremely late diagnosis or fatal outcome amid high loads, which are often the case with athletes and military servicemen. It is necessary to significantly expand the training program in residency and on the cycles of improvement of doctors in the direction of hereditary diseases in each specialty.

Megaconial congenital muscular dystrophy: Same novel homozygous mutation in CHKB gene in two unrelated Chinese patients

2020 ◽  
Vol 30 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Sophelia HS Chan ◽  
Ronnie SL Ho ◽  
PL Khong ◽  
Brian HY Chung ◽  
Mandy HY Tsang ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Congenital Muscular Dystrophy ◽  
Chinese Patients ◽  
Homozygous Mutation

Merosin-deficient congenital muscular dystrophy: A novel homozygous mutation in the laminin-2 gene

2015 ◽  
Vol 22 (12) ◽  
pp. 1983-1985 ◽  
Author(s):  
Clinton Turner ◽  
Rachael Mein ◽  
Cynthia Sharpe ◽  
Donald R. Love
Keyword(s):  
Muscular Dystrophy ◽  
Congenital Muscular Dystrophy ◽  
Homozygous Mutation

scholarly journals Deleterious Facial Effects Caused by Noninvasive Ventilation Mask Early Treatment, in Congenital Muscular Dystrophy

2021 ◽  
Author(s):  
David Andrade ◽  
Maria-João Palha ◽  
Ana Norton ◽  
Viviana Macho ◽  
Rui Andrade ◽  
...  
Keyword(s):  
Noninvasive Ventilation ◽  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Neuromuscular Disorders ◽  
Congenital Muscular Dystrophy ◽  
Neuromuscular Diseases ◽  
General Term ◽  
Morphological Alterations ◽  
Progressive Muscle Weakness ◽  
Bilevel Positive Airway Pressure

Neuromuscular disorders is a general term that encompasses a large number of diseases with different presentations. Progressive muscle weakness is the predominant condition of these disorders. Respiratory failure can occur in a significant number of diseases. The use of devices to assist ventilation is quite frequent in these types of patients. Noninvasive ventilation can be applied by various means, including nasal, oronasal, or facial masks. Masks, type bilevel positive airway pressure, continuous positive airway pressure, and similar are generally supported on the maxilla. Oral health in pediatric neuromuscular diseases has some peculiar aspects that we must consider in these patients’ follow-up. Based on a clinical case, this chapter provides a better understanding of these patients. It will focus on the oral and maxillofacial morphological alterations and preventive measures and strategies for oral pathologies management in this population. Despite always aiming at esthetics, treating these patients should always prioritize the possibilities of improving the oral and general functions of the body.

Sign in / Sign up

Export Citation Format

Share Document