Genetic epidemiology of autosomal recessive hypercholesterolemia in Sicily: Identification by next-generation sequencing of a new kindred

2018 ◽  
Vol 12 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Rossella Spina ◽  
Davide Noto ◽  
Carlo M. Barbagallo ◽  
Roberto Monastero ◽  
Valeria Ingrassia ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Epidemiology ◽  
Autosomal Recessive ◽  
Next Generation ◽  
Autosomal Recessive Hypercholesterolemia ◽  
Generation Sequencing

Diagnostic value of a combination of next-generation sequencing, chorioretinal imaging and metabolic analysis: lessons from a consanguineous Chinese family with gyrate atrophy of the choroid and retina stemming from a novel OAT variant

2018 ◽  
Vol 103 (3) ◽  
pp. 428-435 ◽  
Author(s):  
Junting Huang ◽  
Jiewen Fu ◽  
Shangyi Fu ◽  
Lisha Yang ◽  
Kailai Nie ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Low Income ◽  
Autosomal Recessive ◽  
Diagnostic Value ◽  
Consanguineous Marriage ◽  
Chinese Family ◽  
Next Generation ◽  
Gyrate Atrophy ◽  
Metabolic Analysis ◽  
Generation Sequencing

Background/AimGyrate atrophy of the choroid and retina (GACR) is an extremely rare autosomal recessive inherited disorder characterised by progressive vision loss. To identify the disease-causing gene in a consanguineous Chinese pedigree with GACR, we aimed to accurately diagnose patients with GACR through a combination of next-generation sequencing (NGS) genetic diagnosis, clinical imaging and amino acid metabolic analysis.MethodsA consanguineous Chinese pedigree with GACR, including two patients, was recruited and a comprehensive ophthalmological evaluation was performed. DNA was extracted from a proband and her family members, and the sample from the proband was analysed using targeted NGS. Variants ‎detected by NGS were confirmed by Sanger sequencing and subjected to segregation analysis. Tandem mass spectrometry (MS/MS) was subsequently performed for metabolic assessment.ResultsWe identified a ‎novel, deleterious, homologous ornithine aminotransferase (OAT) variant, c.G248A: p.S83N, which contributes to ‎the progression of GACR in patients. Our results showed that the p.S83N autosomal recessive ‎variant of OAT is most likely ‎pathogenic, with changes in protein stability drastically decreasing functionality. MS/MS verified that ornithine levels in patients were significantly elevated.ConclusionsRecruitment of a third-degree first cousin consanguineous marriage family with GACR allowed us to identify a novel pathogenicOATvariant in the Chinese population, broadening the mutation spectrum. Our findings reported the diagnostic value of a combination of NGS, retinal imaging and metabolic analysis of consanguineous marriage pedigrees in low-income/middle-income and low-incidence countries, including China, and may help to guide accurate diagnosis and ‎treatment of this disease.

Clinical Spectrum and Molecular Pathophysiology of Shwachman-Diamond Syndrome

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. SCI-34-SCI-34
Author(s):  
Akiko Shimamura
Keyword(s):  
Next Generation Sequencing ◽  
Autosomal Recessive ◽  
Conflicts Of Interest ◽  
Diagnostic Algorithm ◽  
Next Generation ◽  
Recessive Mutations ◽  
Pancreatic Dysfunction ◽  
Shwachman Diamond Syndrome ◽  
Molecular Pathophysiology ◽  
Generation Sequencing

Abstract Shwachman-Diamond Syndrome (SDS) is an inherited marrow failure syndrome associated with exocrine pancreatic dysfunction and leukemia predisposition. SDS patients may also manifest additional non-hematologic abnormalities. Autosomal recessive mutations in the SBDS gene are found in over 90 percent of patients fitting the classical clinical phenotype of SDS. The advent of genetic testing has revealed an unexpectedly broad range of SDS phenotypes. Through the Shwachman-Diamond Syndrome Registry, we found that diagnosis may be obscured by cryptic or non-classical presentations of SDS. The timely diagnosis of SDS carries profound ramifications for medical management and treatment. We are developing assays utilizing massively parallel next generation sequencing to address this challenging diagnostic problem. Clinical applications of next generation sequencing to the diagnostic algorithm for marrow failure or myelodysplastic syndrome and implications for medical treatment will be explored. Disclosures: No relevant conflicts of interest to declare.

Next-generation sequencing for molecular diagnosis of autosomal recessive polycystic kidney disease

Gene ◽  
2016 ◽  
Vol 591 (1) ◽  
pp. 214-226 ◽  
Author(s):  
Burhan M. Edrees ◽  
Mohammad Athar ◽  
Faisal A. Al-Allaf ◽  
Mohiuddin M. Taher ◽  
Wajahatullah Khan ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Molecular Diagnosis ◽  
Autosomal Recessive ◽  
Next Generation ◽  
Polycystic Kidney ◽  
Generation Sequencing

scholarly journals Next-generation sequencing confirms the implication ofSLC24A1in autosomal-recessive congenital stationary night blindness

2016 ◽  
Vol 89 (6) ◽  
pp. 690-699 ◽  
Author(s):  
M. Neuillé ◽  
S. Malaichamy ◽  
M. Vadalà ◽  
C. Michiels ◽  
C. Condroyer ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Night Blindness ◽  
Autosomal Recessive ◽  
Congenital Stationary Night Blindness ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Molecular etiology of hereditary deafness using next generation sequencing in northwest China

2020 ◽  
Author(s):  
Suyang Wang ◽  
Shujuan Li ◽  
Wenjuan Ding ◽  
Xiaowen Liu ◽  
Yiming Zhu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Autosomal Recessive ◽  
Family Members ◽  
Northwest China ◽  
Control Group ◽  
Next Generation ◽  
Blood Samples ◽  
Hereditary Deafness ◽  
Molecular Etiology ◽  
Generation Sequencing

Abstract Objective: To analyze the molecular etiology of 92 hereditary deafness families and explore the genetic mechanism of newly identified genes in deafness heritability. Methods: We analyzed the medical history, audiology, imaging, and physical examination data of 92 probands and their family members. Probands were selected from the hereditary deafness database; they did not have any of the common genetic mutation sites. Genomic DNA was extracted from blood samples and next generation sequencing was performed on an Illumina platform, followed by co-segregation analysis of family members. The control group included the clinical data and blood samples from 207 normal hearing people. Results: Among the 92 samples, 30 homozygous variants were identified in 29 autosomal recessive hereditary deafness families, including 6 reported mutations and 26 novel mutations. Among them, MYO15A was the most frequently detected (6/92), followed by mutations in CDH23, OTOF, FGF3 (3/92 each), MYO7A, SLC26A4, MYO6 (2/92 each), BSND, CLDN14, DFNB59, ILDR1, LHFPL5, LRTOMT, TMPRSS3, TPRN, USH1C, and LOXHD1 (1/92 each). Conclusion: In patients with autosomal recessive deafness, the MYO15A, CDH23, OTOF, and FGF3 genes could be used as candidate genes for conventional genetic studies in northwest China.

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