scholarly journals Further Evidence of a Recessive Variant in COL1A1 as an Underlying Cause of Ehlers–Danlos Syndrome: A Report of a Saudi Founder Mutation

2021 ◽  
Author(s):  
Ahmad Almatrafi ◽  
Jamil A. Hashmi ◽  
Fatima Fadhli ◽  
Asma Alharbi ◽  
Sibtain Afzal ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Homozygous Mutation ◽  
Connective Tissues ◽  
Ehlers Danlos Syndrome ◽  
Col1a1 Gene ◽  
Homozygous Variant ◽  
Whole Exome ◽  
The One ◽  
Danlos Syndrome ◽  
Autosomal Recessive Manner

AbstractEhlers–Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous disorder of soft connective tissues. The hallmark clinical features of the EDS are hyperextensible skin, hypermobile joints, and fragile vessels. It exhibits associated symptoms including contractures of muscles, kyphoscoliosis, spondylodysplasia, dermatosparaxis, periodontitis, and arthrochalasia. The aim of this study is to determine the exact subtype of EDS by molecular genetic testing in a family segregating EDS in an autosomal recessive manner. Herein, we describe a family with two individuals afflicted with EDS. Whole exome sequencing identified a homozygous missense mutation (c.2050G > A; p.Glu684Lys) in the COL1A1 gene in both affected individuals, although heterozygous variants in the COL1A1 are known to cause EDS. Recently, only one report showed homozygous variant as an underlying cause of the EDS in two Saudi families. This is the second report of a homozygous variant in the COL1A1 gene in a family of Saudi origin. Heterozygous carriers of COL1A1 variant are asymptomatic. Interestingly, the homozygous variant identified previously and the one identified in this study are same (c.2050G > A). The identification of a unique homozygous mutation (c.2050G > A) in three Saudi families argues in favor of a founder effect.

scholarly journals Geno-phenotypic characteristics of Ehlers–Danlos syndrome: difficulties of disease type identification and approaches to pathogenetic treatment

2021 ◽  
Vol 66 (1) ◽  
pp. 22-30
Author(s):  
E. A. Nikolaeva ◽  
A. N. Semyachkina
Keyword(s):  
Connective Tissue ◽  
Clinical Symptoms ◽  
Molecular Genetic ◽  
Symptomatic Treatment ◽  
Pathological Process ◽  
Social Adaptation ◽  
Molecular Defect ◽  
Ehlers Danlos Syndrome ◽  
Pathogenetic Therapy ◽  
Danlos Syndrome

Veltischev Researchand Clinical Institutefor Pediatricsofthe Pirogov Russian National Research Medical University, Moscow, Russia The article presents modern data on the most common monogenic connective tissue disease – Ehlers–Danlos syndrome. The authors describe two previous classifications of the syndrome: Berlin (1988) classification, which distinguishes 11 types of the disease, and Beyton (1998) classification, which includes 6 types of the syndrome and takes into account the results of molecular genetic studies. Particular attention is paid to a new classification, proposed by the International Consortium in 2017. This classification is based on the clinical and molecular genetic data and unites 13 types of Ehlers–Danlos syndrome, divided in 7 groups (A–G), depending on the main molecular defect. This defect determines the violation of various collagen structures (primary, spatial, cross-linking) and others constituents of the connective tissue (myomatrix, glycosaminoglycans, complement component, etc.). The classification provides general clinical symptoms for all types of the disease and comprehensive information on the specific signs of each of the 13 types of the syndrome.The authors discuss approaches to the pathogenetic therapy of the syndrome, the possibilities of symptomatic treatment, including both medications of different spectrum of action, and physiotherapeutic measures, exercise therapy. The complex of the listed therapeutic measures is aimed at stabilizing the main pathological process, preventing complications, improving the patient’s quality of life and social adaptation. The authors emphasize that correct patient management, targeted medical supervision and medical genetic counseling requires molecular genetic verification of the diagnosis.

Clinical and genetic parallels of the classification and diagnosis of Ehlers-Danlos syndrome

2021 ◽  
pp. 14-26
Author(s):  
Д.Д. Надыршина ◽  
А.В. Тюрин ◽  
Э.К. Хуснутдинова ◽  
Р.И. Хусаинова
Keyword(s):  
Genetic Counseling ◽  
Family Medicine ◽  
Genetic Basis ◽  
Molecular Genetic ◽  
Hereditary Disease ◽  
Orphan Diseases ◽  
Ehlers Danlos Syndrome ◽  
General Medical Practice ◽  
Molecular Genetic Basis ◽  
Danlos Syndrome

Статья посвящена обсуждению подходов к классификации и обзору доступных литературных данных о клинической вариабельности и молекулярно-генетических основах патогенеза редкого наследственного заболевания - синдрома Элерса-Данло. Представленный обзор расширит представление о патогенезе и позволит оптимизировать диагностику данного синдрома, определить тактику лечения и медико-генетического консультирования отягощенных семей как клиническим генетикам, специалистам в области изучения орфанных заболеваний, так и врачам терапевтам, специалистам семейной медицины и общей врачебной практики. The article is devoted to the discussion of approaches to the classification and review of the available literature data on clinical variability and the molecular genetic basis of the pathogenesis of a rare hereditary disease - Ehlers-Danlos syndrome. The presented review will expand the understanding of the pathogenesis and allow to optimize the diagnosis of this syndrome, to determine the tactics of treatment and medical and genetic counseling of burdened families, both to clinical geneticists, specialists in the study of orphan diseases, and to general practitioners, specialists in family medicine and general medical practice.

scholarly journals RETRACTED: Ehlers-Danlos syndrome caused by the c.934C>T, p. Arg312Cys mutation in COL1A1 gene: an Italian family without cardiovascular events

2018 ◽  
Vol 24 (9) ◽  
Author(s):  
Francesca Cortini ◽  
Barbara Marinelli ◽  
Manuela Seia ◽  
Agostino Seresini ◽  
Alessandra Bassotti
Keyword(s):  
Cardiovascular Events ◽  
Ehlers Danlos Syndrome ◽  
Col1a1 Gene ◽  
Italian Family ◽  
Danlos Syndrome

scholarly journals Ehlers-Danlos syndrome caused by the c.934C>T, p. Arg312Cys mutation in COL1A1 gene: an Italian family without cardiovascular events

2018 ◽  
Vol 24 (7) ◽  
Author(s):  
Francesca Cortini ◽  
Barbara Marinelli ◽  
Manuela Seia ◽  
Agostino Seresini ◽  
Alessandra Bassotti
Keyword(s):  
Cardiovascular Events ◽  
Ehlers Danlos Syndrome ◽  
Col1a1 Gene ◽  
Italian Family ◽  
Danlos Syndrome

scholarly journals Identification of a Homozygous PEX26 Mutation in a Heimler Syndrome Patient

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 646
Author(s):  
Youn Jung Kim ◽  
Yuichi Abe ◽  
Young-Jae Kim ◽  
Yukio Fujiki ◽  
Jung-Wook Kim
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Chromosome Study ◽  
Homozygous Mutation ◽  
Sequencing Analysis ◽  
Bilateral Cochlear Implants ◽  
Recessive Mutations ◽  
Whole Exome

This study aimed to identify the molecular genetic etiology of an 8-year-old boy with amelogenesis imperfecta in permanent dentition. Bilateral cochlear implants were placed due to sensorineural hearing loss, and there was no other family member with a similar phenotype. Peripheral blood samples were collected with the understanding and written consent of the participating family members. A constitutional chromosome study was performed for the proband. Genomic DNA was isolated, and whole exome sequencing was performed. A series of bioinformatic analyses were performed with the obtained paired-end sequencing reads, and the variants were filtered and annotated with dbSNP147. There was no abnormality in the constitutional chromosome study. Whole exome sequencing analysis with trio samples identified a homozygous mutation (c.506T>C, p. (Leu169Pro)) in the PEX26 gene. We verified “temperature sensitivity (ts)” of patient-derived Pex26-L169P by expression in pex26 CHO mutant ZP167 cells to determine the effect of the L169P mutation on Pex26 function. The L169P mutation causes a mild ts-cellular phenotype representing the decreased peroxisomal import of catalase. This study supports the finding that the recessive mutations in PEX26 are associated with Heimler syndrome and demonstrates the importance of an early and correct diagnosis.

scholarly journals Ehlers-Danlos syndrome kyphoscoliotic type 2 caused by mutations in the FKBP14 gene: an analysis of five cases

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 502
Author(s):  
Alla Nikolaevna Semyachkina ◽  
Ekaterina Alexandrovna Nikolaeva ◽  
Nailya Mansurovna Galeeva ◽  
Alexander Vladimirovich Polyakov ◽  
Maria Andreevna Kurnikova ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Motor Development ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Molecular Genetic Analysis ◽  
Differential Diagnostics ◽  
Muscular Weakness ◽  
Ehlers Danlos Syndrome ◽  
Danlos Syndrome

Background. This study deals with a rare (orphan) monogenic connective tissue disorder - Ehlers-Danlos syndrome kyphoscoliotic type 2 (EDSKS2). Kyphoscoliotic type 2 Ehlers-Danlos syndrome is an autosomal recessive disorder caused by mutations in the FKBP14 gene (7p14.3), which encodes the FKBP22 protein. According to the 2017 classification, this type is in group seven - collagen spatial structure and cross-linking defects. We present results of clinical examination and molecular genetic analysis for five patients with age varying from two to fifteen years.  Methods. Five patients were examined using clinical and laboratory methods. DNA samples used for the analysis were extracted from whole blood samples using a Wizard® Genomic DNA Purification Kit (Promega, USA) according to the manufacturer's protocol.  Results. The major clinical findings were kyphoscoliosis, early motor development delay, muscular weakness, hypotonia and hearing loss. Molecular genetic analysis detected a homozygous c.362dupC duplication in exon 3 of the FKBP14 gene in all five patients. This mutation is common in various countries. Differential diagnostics were carried out to exclude other Ehlers-Danlos syndrome types and myopathies.  Conclusions. Literature analysis and examination of five EDSKS2 patients demonstrated the involvement of major organs and systems, such as joints, spine, muscles, cardiovascular system, respiratory system, hearing, and vision, into the pathological process. Kidney mobility increases and nephroptosis seems to be secondary caused by muscular weakness. During molecular genetic analysis, to verify EDSKS2 it is recommended to initially search for the c.362dupC duplication, which appears to be common in European countries, including Russia.

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