Nemaline Rods in a Patient of Chorea-Acanthocytosis with a Novel Pathogenic Mutation of VPS13A Gene

2021 ◽  
Vol 69 (6) ◽  
pp. 1848
Author(s):  
Chunlin Zhang ◽  
Ling Jiao ◽  
Qian Zheng ◽  
Lina Zhu
Keyword(s):  
Pathogenic Mutation ◽  
Nemaline Rods

scholarly journals A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Brca1 Gene ◽  
Pathogenic Mutation ◽  
Compound Heterozygous ◽  
Strong Family History ◽  
Breast And Ovarian Cancer ◽  
Pathogenic Mutations ◽  
Increased Risk ◽  
History Of

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.

scholarly journals Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

2021 ◽  
Vol 22 (7) ◽  
pp. 3786
Author(s):  
Andreas Brodehl ◽  
Alexey Meshkov ◽  
Roman Myasnikov ◽  
Anna Kiseleva ◽  
Olga Kulikova ◽  
...  
Keyword(s):  
Medical History ◽  
Splice Site Mutation ◽  
Pathogenic Mutation ◽  
Large Deletion ◽  
Loss Of Function ◽  
Arrhythmogenic Cardiomyopathy ◽  
Site Mutation ◽  
Snp Arrays ◽  
Number Of Patients ◽  
History Of

About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.

scholarly journals SAT0527 COMBINED EFFECT OF COMMON VARIANTS IN EXON 2 OR EXON 3 AND A PATHOGENIC MUTATION IN EXON 10 OF THE MEDITERRANEAN FEVER GENE ON INFLAMMASOME ACTIVATION IN JAPANESE PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1221.2-1221
Author(s):  
T. Koga ◽  
Y. Endo ◽  
K. Furukawa ◽  
K. Agematsu ◽  
A. Yachie ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Japanese Patients ◽  
Pathogenic Mutation ◽  
Inflammasome Activation ◽  
Combined Effects ◽  
Common Variants ◽  
Thoracic Pain ◽  
Exon 2 ◽  
Mediterranean Fever ◽  
Exon 10

Background:Familial Mediterranean fever (FMF) is an autoinflammatory disease that is caused by Mediterranean fever (MEFV) gene mutations. It is characterized by recurrent and self-limiting febrile attacks within a short period. Although the pathologic significance ofMEFVexon 2 or exon 3 common variants in patients with FMF is modest and these variants are usually associated with less severe clinical presentations of FMF (1, 2), their combined effects with pathogenic mutation in exon 10 remain to be evaluated.Objectives:To determine the combined effect of common variants on clinical manifestations and inflammasome activity, we compared the clinical and laboratory characteristics between the coexistence and non-coexistence ofMEFVexon 2 or exon 3 variants in patients with FMF that had a heterozygousMEFVexon 10 mutation.Methods:We excluded patients with FMF that had twoMEFVexon 10 mutations in one or more alleles and those withMEFVvariants in exons other than in exons 2, 3, or 10. Finally, we reviewed 131 Japanese patients with FMF that had a heterozygousMEFVexon 10 mutation, and they were divided into the groups with and withoutMEFVexon 2 or exon 3 variants of 34 and 97, respectively. All enrolled patients had only a heterozygous M694I mutation in exon 10 of theMEFVgene. We measured serum IL-18 levels at remission without febrile attacks in the groups with and withoutMEFVexon 2 or exon 3 variants of 9 and 31, respectively.Results:In the univariate analysis, the group with variants in exon 2 or exon 3 had significantly earlier onset (16.0 years v.s. 20.5 years, p = 0.04), a higher percentage of thoracic pain with febrile attacks (68% v.s. 44%, p = 0.02), a higher frequency of attack (1.0/month v.s. 0.5/month, p = 0.02), and a higher IL-18 level in the serum at remission (606.3 pg/ml v.s. 168.4 pg/ml, p = 0.04, Figure 1) compared to the group without these variants. Importantly, multivariate analyses showed that the coexistence ofMEFVexon 2 or exon 3 variants and an exon 10 mutation was independently and significantly associated with earlier onset of FMF (p = 0.049) and thoracic pain (p = 0.03).Figure 1.Conclusion:Our results suggest that the coexistence ofMEFVexon 2 or exon 3 variants and aMEFVexon 10 mutation has combined effects on inflammasome activation in the Japanese population.References:[1]Migita K, Uehara R, Nakamura Y, et al. Familial Mediterranean fever in Japan. Medicine (Baltimore). 2012 Nov;91(6):337-43.[2]Shinar Y, Livneh A, Langevitz P, Genotype-phenotype assessment of common genotypes among patients with familial Mediterranean fever. J Rheumatol. 2000;27(7):1703.Disclosure of Interests:None declared

Nemaline Rods in Two Young Border Collies with Myopathy

2014 ◽  
Vol 150 (1) ◽  
pp. 92
Author(s):  
M. Dettwiler ◽  
S. Klausmann ◽  
K. Beckmann ◽  
T. Sydler
Keyword(s):  
Nemaline Rods

scholarly journals Novel Pathogenic Mutation Identified in the COL1A2 Gene Presumably as a Cause of Osteogenesis Imperfecta: A Case Report and Literature Review

2016 ◽  
Vol 146 (suppl_1) ◽  
Author(s):  
Jose Scarpa Carniello ◽  
Chuanyong Lu ◽  
Jacqueline Skelton ◽  
Ning Chen ◽  
Alejandro Zuretti
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Osteogenesis Imperfecta ◽  
Pathogenic Mutation ◽  
Col1a2 Gene

scholarly journals Mutations of uncertain significance in heterozygous variants as a possible cause of severe short stature: a case report

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Nami Mohammadian Khonsari ◽  
Sahar Mohammad Poor Nami ◽  
Benyamin Hakak-Zargar ◽  
Tessa Voth
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Hormone Receptors ◽  
Bone Growth ◽  
Synergistic Effects ◽  
Signs And Symptoms ◽  
Bone Age ◽  
Pathogenic Mutation ◽  
Paracrine Factors ◽  
Severe Short Stature

Abstract Background Linear bone growth is achieved by the division of chondrocytes at the growth plate and is regulated by endocrine and paracrine factors such as growth hormone. Mutations that negatively affect chondrogenesis can be a contributor to short stature. One such mutation can occur in the ACAN gene, causing short stature and advanced bone age. Similarly, mutations in growth hormone receptors (GHR) can lead to Laron syndrome (LS), one of the several disorders that are collectively called growth hormone insensitivity syndrome (GHI). Another example is Floating-Harbor syndrome (FHS), a rare autosomal dominant due to mutations in the SRCAP gene that can also result in short stature. Case presentation We report the case of a 6-year-old female with concomitant mutations in the three genes mentioned above. The mutations reported here were found on genetic studies and are usually benign, causing a variant of undetermined significance. However, our patient’s phenotype could only be explained by the compounded effects of pathogenic mutations of these genes. Some of the same mutations were also found in the patient’s father and her paternal grandfather. Both also presented with short stature, though not to the same degree as our patient. While these mutations are often reported to be insignificant, they gave rise to severe short stature and a specific phenotype in the patient when presented together. We think that even though the GHI spectrum is inherited through an autosomal recessive pattern, the sum of these heterozygous mutations resulted in severe short stature despite the limited GHI seen in our patient, the father, and the grandfather, through a rare ACAN and SRCAP mutation that, to our knowledge, has not been previously reported as a pathogenic mutation in the literature. Conclusion We investigated the possible synergistic effects of these variations on exacerbation or masking of the signs and symptoms of GHI with the hope of providing a better understanding of these genes and their function through our rare case.

Sarcoplasmic bodies in distal myopathy compared with nemaline rods

1981 ◽  
Vol 49 (3) ◽  
pp. 341-352 ◽  
Author(s):  
Lars Edström ◽  
Romuald Wroblewsk
Keyword(s):  
Distal Myopathy ◽  
Nemaline Rods

scholarly journals FGFR3 Dimer Stabilization Due to a Single Amino Acid Pathogenic Mutation

2006 ◽  
Vol 356 (3) ◽  
pp. 600-612 ◽  
Author(s):  
Edwin Li ◽  
Min You ◽  
Kalina Hristova
Keyword(s):  
Amino Acid ◽  
Pathogenic Mutation ◽  
Single Amino Acid

Melanocortin-4 Receptor Gene Variation Is Associated with Eating Behavior in Chilean Adults

2015 ◽  
Vol 68 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Javier A. Vega ◽  
Gloria Salazar ◽  
María Isabel Hodgson ◽  
Luis Rodrigo Cataldo ◽  
Macarena Valladares ◽  
...  
Keyword(s):  
Eating Behavior ◽  
Emotional Eating ◽  
Leptin Receptor ◽  
Receptor Gene ◽  
Pathogenic Mutation ◽  
Gene Variation ◽  
Mc4r Gene ◽  
Melanocortin 4 Receptor ◽  
Melanocortin 4 Receptor Gene ◽  
Mc4r Rs17782313

Background/Aims: To evaluate the association between allelic variants of melanocortin receptors -3 and -4 (MC3R and MC4R, respectively) and leptin receptor (LEPR) genes with body mass index (BMI) and eating behavior. Methods: We selected 344 Chilean adults (57.8% women; age 39.1 ± 6.6 years) with a wide variation in BMI (30.3 ± 6.3 kg/m2). The Three-Factor Eating Questionnaire-R18 that measures uncontrolled eating (UE), emotional eating (EE) and cognitive restraint scores was adapted, validated and assessed for association with BMI. Genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism techniques and Taqman assays. Results: Higher EE scores were found in obese vs. non-obese in both men (p = 0.01) and women (p < 0.001). UE scores were significantly associated with BMI only in women (p = 0.002). No significant differences in eating behavior scores or BMI were found by LEPR (rs1137101, rs8179183 and rs1137100 polymorphisms) or MC3R (rs3746619 and rs3827103). Carriers of the C allele for MC4R rs17782313 showed significantly higher scores of UE compared to non-carriers (2.3 ± 0.8 vs. 2.0 ± 0.7; p = 0.02). Additionally, we also report a monogenic case of obesity carrying the pathogenic mutation 449C>T (Thr150Ile) in MC4R gene with no apparent alterations in eating behavior scores. Conclusions: UE scores were higher in C-allele carriers of MC4R-rs17782313 compared to non-carriers.

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