19 research outputs found

    A novel mutation in SEPN1 causing rigid spine muscular dystrophy 1: A Case report

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    Abstract Background Muscular dystrophies are a clinically and genetically heterogeneous group of disorders characterized by variable degrees of progressive muscle degeneration and weakness. There is a wide variability in the age of onset, symptoms and rate of progression in subtypes of these disorders. Herein, we present the results of our study conducted to identify the pathogenic genetic variation involved in our patient affected by rigid spine muscular dystrophy. Case presentation A 14-year-old boy, product of a first-cousin marriage, was enrolled in our study with failure to thrive, fatigue, muscular dystrophy, generalized muscular atrophy, kyphoscoliosis, and flexion contracture of the knees and elbows. Whole-exome sequencing (WES) was carried out on the DNA of the patient to investigate all coding regions and uncovered a novel, homozygous missense mutation in SEPN1 gene (c. 1379 C > T, p.Ser460Phe). This mutation has not been reported before in different public variant databases and also our database (BayanGene), so it is classified as a variation of unknown significance (VUS). Subsequently, it was confirmed that the novel variation was homozygous in our patient and heterozygous in his parents. Different bioinformatics tools showed the damaging effects of the variant on protein. Multiple sequence alignment using BLASTP on ExPASy and WebLogo, revealed the conservation of the mutated residue. Conclusion We reported a novel homozygous mutation in SEPN1 gene that expands our understanding of rigid spine muscular dystrophy. Although bioinformatics analyses of results were in favor of the pathogenicity of the mutation, functional studies are needed to establish the pathogenicity of the variant

    Expanding the molecular and clinical phenotypes of FUT8‐CDG

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    Pathogenic variants in the Golgi localised alpha 1,6 fucosyltransferase, FUT8, cause a rare inherited metabolic disorder known as FUT8-CDG. To date, only three affected individuals have been reported presenting with a constellation of symptoms including intrauterine growth restriction, severe delays in growth and development, other neurological impairments, significantly shortened limbs, respiratory complications, and shortened lifespan. Here, we report an additional four unrelated affected individuals homozygous for novel pathogenic variants in FUT8. Analysis of serum N -glycans revealed a complete lack of core fucosylation, an important diagnostic biomarker of FUT8-CDG. Our data expands both the molecular and clinical phenotypes of FUT8-CDG and highlights the importance of identifying a reliable biomarker for confirming potentially pathogenic variants

    A novel splice site mutation in WAS gene in patient with Wiskott-Aldrich syndrome and chronic colitis: a case report

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    Abstract Background Wiskott-Aldrich syndrome is an X-linked recessive immunodeficiency due to mutations in Wiskott-Aldrich syndrome (WAS) gene. WAS gene is encoded for a multifunctional protein with key roles in actin polymerization, signaling pathways, and cytoskeletal rearrangement. Therefore, the impaired protein or its absence cause phenotypic spectrum of the disease. Since identification of novel mutations in WAS gene can help uncover the exact pathogenesis of Wiskott-Aldrich syndrome, the purpose of this study was to investigate disease causing-mutation in an Iranian male infant suspicious of this disorder. Case presentation The patient had persistent thrombocytopenia from birth, sepsis, and recurrent gastrointestinal bleeding suggestive of both Wiskott-Aldrich syndrome and chronic colitis in favor of inflammatory bowel disease (IBD). To find mutated gene in the proband, whole exome sequencing was performed for the patient and its data showed a novel, private, hemizygous splice site mutation in WAS gene (c.360 + 1G > C). Conclusions Our study found a novel, splice-site mutation in WAS gene and help consider the genetic counselling more precisely for families with clinical phenotypes of both Wiskott-Aldrich syndrome and inflammatory bowel disease and may suggest linked pathways between these two diseases
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