scholarly journals Identification of a New Variant in NLRP3 Gene by Whole Exome Sequencing in a Patient with Cryopyrin-Associated Periodic Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Mahdieh Vahedi ◽  
Nima Parvaneh ◽  
Saeedeh Vahedi ◽  
Mohammad Shahrooei ◽  
Vahid Ziaee
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Joint Pain ◽  
Chromosome 1 ◽  
Periodic Syndrome ◽  
Nlrp3 Gene ◽  
Case Presentation ◽  
Whole Exome ◽  
New Variant ◽  
Novel Variant

Background. NLRP3 gene is located in chromosome 1 and encodes a pyrin-like protein. Mutations in this gene are associated with an autoinflammatory disease, called cryopyrin-associated periodic syndrome (CAPS). Case Presentation. We report a 1-year-old boy who had recurrent urticarial rash since birth and joint pain and swelling. He had a missense mutation c.G1060 T (p.A354S) in exon 5 of the NLRP3 gene which was detected by whole exome sequencing. Conclusion. A novel variant was found in the NLRP3 gene which has not been reported by now.

scholarly journals Whole exome sequencing identified a homozygous novel variant in CEP290 gene causes Meckel syndrome

2019 ◽  
Vol 24 (2) ◽  
pp. 1906-1916 ◽  
Author(s):  
Rui Zhang ◽  
Shaoyun Chen ◽  
Peng Han ◽  
Fangfang Chen ◽  
Shan Kuang ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Meckel Syndrome ◽  
Whole Exome ◽  
Novel Variant

scholarly journals A Novel Missense Variant of TP63 Heterozygously Present in Split-Hand/Foot Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Hao Geng ◽  
Dongdong Tang ◽  
Chuan Xu ◽  
Xiaojin He ◽  
Zhiguo Zhang
Keyword(s):  
Blood Sample ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Peripheral Blood ◽  
Sanger Sequencing ◽  
Missense Variant ◽  
Chinese Family ◽  
Peripheral Blood Sample ◽  
Whole Exome ◽  
Novel Variant

Background. Split-hand/foot malformation (SHFM) is a severe congenital disability mainly characterized by the absence or hypoplasia of the central ray of the hand/foot. To date, several candidate genes associated with SHFM have been identified, including TP63, DLX5, DLX6, FGFR1, and WNT10B. Herein, we report a novel variant of TP63 heterozygously present in affected members of a family with SHFM. Methods. This study investigated a Chinese family, in which the proband and his son suffered from SHFM. The peripheral blood sample of the proband was used to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Postsequencing bioinformatic analyses and Sanger sequencing were conducted to verify the identified variants and parental origins on all family members in the pedigree. Results. By postsequencing bioinformatic analyses and Sanger sequencing, we identified a novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in this family that results in a substitution of methionine with isoleucine, which is probably associated with the occurrence of SHFM. Conclusion. A novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in SHFM was thus identified, which may enlarge the spectrum of known TP63 variants and also provide new approaches for genetic counselling of families with SHFM.

scholarly journals A novel nonsense variant in SUPT20H gene associated with Rheumatoid Arthritis identified by Whole Exome Sequencing of multiplex families

2018 ◽  
Author(s):  
Maëva Veyssiere ◽  
Javier Perea ◽  
Laetitia Michou ◽  
Anne Boland ◽  
Christophe Caloustian ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variants ◽  
P Value ◽  
Macrophage Differentiation ◽  
Extended Pedigrees ◽  
Whole Exome ◽  
New Variant ◽  
Multiplex Families

AbstractThe triggering and development of Rheumatoid Arthritis (RA) is conditioned by environmental and genetic factors. Despite the identification of more than one hundred genetic variants associated with the disease, not all the cases can be explained. Here, we performed Whole Exome Sequencing in 9 multiplex families (N=30) to identify rare variants susceptible to play a role in the disease pathogenesis. We pre-selected 73 genes which carried rare variants with a complete segregation with RA in the studied families. Follow-up linkage and association analyses with pVAAST highlighted significant RA association of 24 genes (p-value < 0.05 after 106 permutations) and pinpointed their most likely causal variant. We re-sequenced the 10 most significant likely causal variants (p-value ≤ 0.019 after 106 permutations) in the extended pedigrees and 9 additional multiplex families (N=110). Only one SNV in SUPT20H, c.73T>A (p.Lys25*), presented a complete segregation with RA in an extended pedigree with early-onset cases. In summary, we identified in this study a new variant associated with RA in SUPT20H gene. This gene belongs to several biological pathways like macro-autophagy and monocyte/macrophage differentiation, which contribute to RA pathogenesis. In addition, these results showed that analyzing rare variants using a family-based approach is a strategy that allows to identify RA risk loci, even with a small dataset.Author summaryRheumatoid arthritis (RA) is one of the most frequent auto-immune disease in the world. It causes joint swellings and pains which can lead to mobility impairment. To date, the scientific community has identified a hundred genes carrying variants predisposing to RA, in addition to the major gene HLA-DRB1. However, they do not explain all cases of RA. By examining nine families with multiple RA cases, we identified a new rare nonsense variant in SUPT20H gene, c.73T>A (p.Lys25*). This finding is supported by the literature as the SUPT20H gene regulates several biological functions, such as macro-autophagy or monocyte/macrophage differentiation, that contribute to RA pathogenesis.

276 A new face for an old foe?

2018 ◽  
Vol 89 (10) ◽  
pp. A40.3-A40 ◽  
Author(s):  
Sangha Gavinda ◽  
Bron Anthony ◽  
Donaghy Michael ◽  
Evans Cerys ◽  
Hardcastle Alison ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Family Members ◽  
Calcium Sensitivity ◽  
Actin Binding ◽  
Cranial Neuropathy ◽  
Limb Weakness ◽  
Proteolytic Cascade ◽  
Whole Exome ◽  
Novel Variant

BackgroundMutations in the protein gelsolin result in hereditary systemic amyloidosis, characterised by onset of corneal lattice dystrophy in the third decade, a slowly progressive cranial neuropathy and cutis laxa. To date four dominantly inherited gelsolin mutations have been identified, two mutations resulting in the classical syndrome and two mutations resulting in renal-predominant amyloidosis.MethodsWe identified a family in which four individuals in three generations presented with corneal lattice dystrophy and neurological symptoms. Detailed clinical neurological and ophthalmological assessment and investigations including neurophysiology and imaging were performed. Whole exome sequencing was undertaken in three family members.ResultsWhole exome sequencing revealed a novel variant in the gelsolin gene (c. G1738A; p. E580K), dominantly inherited and predicted to be pathogenic. Examination, neurophysiological testing and imaging revealed the presence of distal upper limb weakness and wasting, corneal lattice dystrophy and cervical myelopathy in all affected family members.ConclusionThe E580K mutation described in this family is in a conserved calcium-sensitive actin-binding domain that displays sequence homology with other actin-depolymerising proteins. Mutations in this domain may result in abnormal gelsolin-actin interactions and changes in calcium sensitivity may render the protein susceptible to the same aberrant proteolytic cascade as with other known mutations.

scholarly journals Whole-Exome Sequencing Identified a Novel Variant (C.405_422+39del) in DSP Gene in an Iranian Pedigree with Familial Dilated Cardiomyopathy

2021 ◽  
Vol 10 (2) ◽  
pp. 280-287
Author(s):  
Yeganeh Eshaghkhani ◽  
Arezoo Mohamadifar ◽  
Mostafa Asadollahi ◽  
Mahdieh Taghizadeh ◽  
Arezou Karamzade ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Familial Dilated Cardiomyopathy ◽  
Whole Exome ◽  
Novel Variant

scholarly journals A Novel Variant of SMARCB1 in Rare Familial Schwannomatosis Identified by Whole-Exome Sequencing and Genotype-Phenotype Correlation Analysis.

2021 ◽  
Author(s):  
Conghui Wang ◽  
Yuqiong Chai ◽  
Xuechao Zhao ◽  
Qianqian Li ◽  
Chen Chen ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Suppressor Gene ◽  
Loss Of Function ◽  
Phenotype Correlation ◽  
Rhabdoid Tumour ◽  
Whole Exome ◽  
Mutation Database ◽  
Novel Variant ◽  
Autosomal Dominant Inheritance Pattern

Abstract Background: Variants in the tumor suppressor gene SMARCB1 could cause different conditions. In some cases, germline and somatic variants in SMARCB1 are implemented in schwannomatosis. But the genotype and phenotype correlation for variants in SMARCB1 has not been determined.Methods: A Chinese schwannomatosis family with an autosomal dominant inheritance pattern was recruited. Whole-exome sequencing (WES) was performed to discover the causative variant, followed by Sanger sequencing. We evaluated the Human Gene Mutation Database (HGMD) regarding SMARCB1 variants and validated associated phenotype records to assess phenotype-genotype relationships. Results: A novel deletion variant c.885_896delGAAGCTGTGCTC p.(295_299del） in SMARCB1 was identified in the affected family members and cosegregated with phenotypes in the pedigree. About 51.1% of variants in SMARCB1 located in Snf5 subunit, 80.7% of variants were loss-of-function (LOF) variants, and more variants located in the Snf5 subunit of SMARCB1 in Rhabdoid tumour (67.8%) than that in schwannomatosis (25.7%).Conclusions: Our study expands the variant spectrum of SMARCB1 and the genetic background of schwannomatosis, confirms the clinical indications for genetic screening of the SMARCB1 gene, and has implications for genetic counseling in this disease.

Identification of a novel variant in GPR56/ADGRG1 gene through whole exome sequencing in a consanguineous Pakistani family

2021 ◽  
Vol 94 ◽  
pp. 8-12
Author(s):  
Shumaila Zulfiqar ◽  
Muhammad Tariq ◽  
Shafaq Ramzan ◽  
Ayaz Khan ◽  
Muhammad Sher ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Pakistani Family ◽  
Whole Exome ◽  
Novel Variant

scholarly journals Clinical and whole-exome sequencing findings in two siblings from Hani ethnic minority with congenital glycosylation disorders

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhen Zhang ◽  
Ti-Long Huang ◽  
Jing Ma ◽  
Wen-Ji He ◽  
Huaiyu Gu
Keyword(s):  
Ethnic Minority ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Population ◽  
Novel Mutation ◽  
Genetic Disorders ◽  
Central Nervous System Involvement ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Whole Exome

Abstract Background PMM2-CDG, is the most common N-linked glycosylation disorder and subtype among all CDG syndromes, which are a series of genetic disorders involving the synthesis and attachment of glycoproteins and glycolipid glycans. The mutations of PMM2-CDG might lead to the loss of PMM2, which is responsible for the conversion of mannose 6- phosphate into mannose 1-phosphate. Most patients with PMM2-CDG have central nervous system involvement, abnormal coagulation, and hepatopathy. The neurological symptoms of PMM2-CDG are intellectual disability (ID), cerebellar ataxia, and peripheral neuropathy. Now, over 100 new CDG cases have been reported. However, each type of CDG is very rare, and CDGs are problematic to diagnose. In addition, few CDGs have been reported in the Chinese population. Case presentation Here we present a Hani ethnic minority family including two siblings with congenital glycosylation disorders. Whole-exome sequencing revealed compound heterozygous for one novel mutation (c.241–242 del variant) and previously reported mutation (c.395 T > C) in gene of PMM2. Two mutations were found in proband and her sibling by whole-exome sequencing. The mutations were identified in this family by Sanger sequencing and no mutations were detected in the normal control. Conclusions This is the first report to describe mutations in two siblings of Hani ethnic minority which is one of five ethnic groups found only in Yunnan with a population of more than 1 million.

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