Aicardi-Goutières Syndrome due to a SAMHD1 Mutation Presenting with Deep White Matter Cysts

2021 ◽  
pp. 1-7
Author(s):  
Barbara Oleksy ◽  
Hanna Mierzewska ◽  
Jolanta Tryfon ◽  
Maria Wypchło ◽  
Krystyna Wasilewska ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Interferon Response ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Type I ◽  
Deep White Matter ◽  
Temporal Lobes ◽  
Whole Exome ◽  
Polish Patient

We report on the first Polish patient diagnosed with the Aicardi-Goutières syndrome 5 (AGS5). AGS is caused by mutations in one of 9 genes (<i>TREX1</i>, <i>RNASEH2A</i>, <i>RNASEH2B</i>, <i>RNASEH2C</i>, <i>SAMHD1</i>, <i>ADAR</i>, <i>IFIH</i>, <i>LSM11</i>, <i>RNU7-1</i>) which stimulate the type I interferon response. The diagnosis was confirmed by identifying a compound heterozygous mutation p.(Phe165Ser)/p.(Gln235*) in the <i>SAMHD1</i> gene using whole-exome sequencing. The cystic lesions in the temporal lobes are an uncommon finding in the presented patient carrying a <i>SAMHD1</i> mutation. Reporting new cases expands the range of phenotypes and plays the crucial role in understanding the AGS pathogenesis and creates new therapy approaches.

scholarly journals Mutation analysis of SLC37A4 in a patient with glycogen storage disease-type Ib

2019 ◽  
Vol 47 (12) ◽  
pp. 5996-6003
Author(s):  
Yamei Zhang ◽  
Huihui Sun ◽  
Naijun Wan
Keyword(s):  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Gene Mutations ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Type I

Objective The aim of the study was to investigate the relationship between SLC37A4 gene mutation and clinical phenotype in a patient with glycogen storage disease-type I. Methods The clinical data of one patient with glycogen storage disease-type I accumulation syndrome and the results of SLC37A4 gene testing were analyzed. DNA from peripheral blood was used to analyze the SLC37A4 mutations of the patient and his parents. Results The patient carried a compound heterozygous mutation of SLC37A4, his mother was heterozygous for the c.572C > T (p.P191L) mutation, and his father was heterozygous for the c.359C > T (p.P120L) mutation. Conclusion The patient had two gene mutations: c.359C > T (p.P120L), which is closely related to glycogen storage disease-type I, and c.572C > T (p.P191L), which is a known mutation in the disease.

scholarly journals Identification of Novel ADGRV1 and KCNC2 Variants Using Whole-Exome Sequencing in Two Colombian Patients with Usher and Encephalopathy Syndromes

2021 ◽  
Author(s):  
Estephania Candelo ◽  
Lorena Diaz-Ordoñez ◽  
Rafael Pacheco ◽  
Emelina Ruiz ◽  
Harry Pachajoa
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Usher Syndrome ◽  
Epileptic Encephalopathy ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Epilepsy Syndrome ◽  
Compound Heterozygous ◽  
Whole Exome ◽  
Excellent Method

Abstract Introduction: Usher syndrome has a broad phenotypic and genotypic spectrum. Developmental and epileptic encephalopathy-52 (DEE52) is a sever autosomal recessive seizure disorder that is characterized by infantile onset of refractory seizures, consequently resulting in delayed global development. This study aimed to describe the clinical features and to investigate the four variants identified in a Colombian family with Usher syndrome and KCNC2 encephalopathy syndrome.Methods and Results: We present a case of a family with two clinically relevant phenotypes: a mother with a compound heterozygous mutation causing Usher Syndrome, type IIC (USH2C) and her 15-year-old son who carried one heterozygous variant in the KCNC2 gene (p.P470S) and two cis mutations (p.V2927I and p.Q4955EfsTer10) in the ADGRV1 gene segregated from his mother, and a second non-disrupted allele. Owing to this, the boy did not present with USH2C but presented a developmental epilepsy syndrome. His younger sibling was unaffected, although he did inherit the trans mutation in a single pathogenic allele from his mother.Discussion and Conclusion: Whole-exome sequencing helps detect genes related to known and novel hearing loss and seizure syndrome. However, familiar segregation studies are an excellent method to clarify genotype-phenotype correlation in families, where multiple genes of clinically relevant have been identified. This method helps determine the genotype-phenotype relationship of a disease, which is associated with the clinical presentation and determines the pathogenicity of variants that are classified as variants of uncertain clinical significance.

scholarly journals Novel compound heterozygous mutation in WEE2 is associated with fertilization failure: case report of an infertile woman and literature review

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ye Tian ◽  
Guojie Wang ◽  
Jin Wang ◽  
Xiaohuan Mu ◽  
Haixia Chen ◽  
...  
Keyword(s):  
Donor Site ◽  
Oocyte Retrieval ◽  
Controlled Ovarian Hyperstimulation ◽  
Infertile Woman ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Fertilization Failure ◽  
Whole Exome ◽  
History Of

Abstract Background Fertilization failure after intracytoplasmic sperm injection continues to affect couples and the etiology is not well-understood. Case presentation We characterized a couple with 2-year history of primary unexplained infertility. Three different assisted reproduction attempts (IVF + rescue ICSI, ICSI and ICSI-AOA) showed repeated fertilization failure for MII oocyte retrieval after controlled ovarian hyperstimulation. After whole-exome sequencing and sanger sequencing of the couple and their family members, variant pathogenicity was assessed using SIFT, PolyPhen2, Mutation Taster, and Human Splicing Finder software. We identified novel compound heterozygous mutations, c.1535 + 3A > G and c.946C > T (p. Leu316Phe), in WEE2 in the female proband. Trios analysis of the variations revealed an autosomal recessive pattern. c.1535 + 3A > G in WEE2 was predicted to break the wild-type donor site and affect splicing, and the missense mutation c.946C > T (p. Leu316Phe) of WEE2 was predicted to be pathogenic. Conclusion A novel compound heterozygous mutation in WEE2 was identified in an infertile female who experienced repeated fertilization failure even after ICSI-AOA. These novel mutations in WEE2 provided genetic evidence for fertilization failure.

scholarly journals Genetic, Prenatal, and Preimplantation Genetic Diagnosis of Glutaric Aciduria Type I

2021 ◽  
Vol 3 (1) ◽  
pp. 397-404
Author(s):  
He B ◽  
Wang L ◽  
Wu Q ◽  
Song C ◽  
Li W ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Treatment Guidelines ◽  
Genetic Diagnosis ◽  
Monogenic Disease ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Type I ◽  
Preimplantation Genetic Testing

Purpose: Glutaric Acid Type I (GA-I) is an inherited metabolic disorder. Although the treatment guidelines for GA-I were established a decade ago, they cannot block the vertical heredity. We aim to apply genetic methods to block the inheritance of GA-I and verifies the efficiency of Next-Generation Sequencing (NGS)-based Preimplantation Genetic Testing for Monogenic disease (PGT-M) of GA-I.Materials and methods: A non-consanguineous Chinese family was diagnosed with GA-I by Sanger sequencing. PGT-M and prenatal diagnosis (PND) were performed for the carrier. 5 blastocysts were used for the trophectoderm biopsy. After Whole-Genome Amplification (WGA), the WGA products were used for Sanger sequencing, NGS-based PGT-M and PGT-A. Sanger sequencing-based PND was performed in second trimester to confirm the results of PGT-M.Results: A compound heterozygous mutation was diagnosed in the GCDH gene with co-segregation. One is [c.533G>A (p.G178E)] and another is [c.914C>T (p.S305L)]. 2 blastocysts were diagnosed as normal and one of them was transferred into the mother’s uterus. Finally, a healthy female was born 39 weeks after transplantation.Conclusion: Our study successfully applied NGS-based PGT-M to avoid GA-I and highlights the efficiency of genetic diagnoses. It has significant implications on genetic counseling and genetic diagnosis for GA-I.

scholarly journals Novel Compound Heterozygous Mutation in TRAPPC9 Gene: The Relevance of Whole Genome Sequencing

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 557
Author(s):  
Maria Isabel Alvarez-Mora ◽  
Jordi Corominas ◽  
Christian Gilissen ◽  
Aurora Sanchez ◽  
Irene Madrigal ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Missense Variant ◽  
Autism Spectrum ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Whole Genome ◽  
Whole Exome ◽  
Considerable Impact

Advances in high-throughput technologies and its implementation worldwide have had a considerable impact on the elucidation of the molecular causes underlying neurodevelopmental psychiatric disorders, especially for autism spectrum disorder and intellectual disability (ID). Nevertheless, etiology remains elusive in close to 50% of cases, even in those families with multiple affected individuals, strongly hinting at a genetic cause. Here we present a case report of two siblings affected with severe ID and other comorbidities, who embarked on a genetic testing odyssey until diagnosis was reached by using whole genome sequencing (WGS). WGS identified a maternally inherited novel missense variant (NM_031466.7:c.1037G > A; p.Gly346Glu) and a paternally inherited 90 kb intragenic deletion in TRAPPC9 gene. This report demonstrates the clinical utility of WGS in patients who remain undiagnosed after whole exome sequencing.

scholarly journals Whole-Exome Sequencing Identified a Novel Compound Heterozygous Mutation of LRRC6 in a Chinese Primary Ciliary Dyskinesia Patient

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Lv Liu ◽  
Hong Luo
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Primary Ciliary Dyskinesia ◽  
Premature Stop Codon ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Mrna Levels ◽  
Whole Exome ◽  
Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a clinical rare peculiar disorder, mainly featured by respiratory infection, tympanitis, nasosinusitis, and male infertility. Previous study demonstrated it is an autosomal recessive disease and by 2017 almost 40 pathologic genes have been identified. Among them are the leucine-rich repeat- (LRR-) containing 6 (LRRC6) codes for a 463-amino-acid cytoplasmic protein, expressed distinctively in motile cilia cells, including the testis cells and the respiratory epithelial cells. In this study, we applied whole-exome sequencing combined with PCD-known genes filtering to explore the genetic lesion of a PCD patient. A novel compound heterozygous mutation in LRRC6 (c.183T>G/p.N61K; c.179-1G>A) was identified and coseparated in this family. The missense mutation (c.183T>G/p.N61K) may lead to a substitution of asparagine by lysine at position 61 in exon 3 of LRRC6. The splice site mutation (c.179-1G>A) may cause a premature stop codon in exon 4 and decrease the mRNA levels of LRRC6. Both mutations were not present in our 200 local controls, dbSNP, and 1000 genomes. Three bioinformatics programs also predicted that both mutations are deleterious. Our study not only further supported the importance of LRRC6 in PCD, but also expanded the spectrum of LRRC6 mutations and will contribute to the genetic diagnosis and counseling of PCD patients.

scholarly journals Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios

2021 ◽  
Vol 12 ◽  
Author(s):  
Shin-Yu Lin ◽  
Gwo-Tsann Chuang ◽  
Chien-Hui Hung ◽  
Wei-Chou Lin ◽  
Yung-Ming Jeng ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Neonatal Death ◽  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Early Neonatal Death ◽  
Renal Tubular Dysgenesis ◽  
Whole Exome ◽  
Renal Tubular

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G &gt; T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally.

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