Review for "DEVELOPMENT OF A NEW EXPANDED NEXT‐GENERATION SEQUENCING PANEL FOR GENETIC DISEASES INVOLVED IN DYSLIPIDEMIA"

AimsThe causes of intellectual disability, which affects 1%–3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases.MethodsWhole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes.ResultsWe present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose.ConclusionsThe accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.

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Next generation sequencing: Coping with rare genetic diseases in China

Intractable & Rare Diseases Research ◽

10.5582/irdr.2016.01020 ◽

2016 ◽

Vol 5 (3) ◽

pp. 140-144 ◽

Cited By ~ 5

Author(s):

David S Cram ◽

Daixing Zhou

Keyword(s):

Next Generation Sequencing ◽

Genetic Diseases ◽

Next Generation ◽

Rare Genetic Diseases ◽

Generation Sequencing

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Neonatal Metabolic Acidosis in the Neonatal Intensive Care Unit: What Are the Genetic Causes?

Frontiers in Pediatrics ◽

10.3389/fped.2021.727301 ◽

2021 ◽

Vol 9 ◽

Author(s):

Haiyan Ma ◽

Zezhong Tang ◽

Feifan Xiao ◽

Long Li ◽

Yangfang Li ◽

...

Keyword(s):

Intensive Care ◽

Metabolic Acidosis ◽

Next Generation Sequencing ◽

Neonatal Intensive Care ◽

Treatment Options ◽

Genetic Diseases ◽

Clinical Signs ◽

Next Generation ◽

Genetic Causes ◽

Generation Sequencing

Neonatal metabolic acidosis (NMA) is a common problem, particularly in critically ill patients in neonatal intensive care units (NICUs). Complex etiologies and atypical clinical signs make diagnosis difficult; thus, it is crucial to investigate the underlying causes of NMA rapidly and provide disorder-specific therapies. Our study aims to provide an overview of the genetic causes of NMA in patients from NICUs. We performed next-generation sequencing (NGS) on neonates with NMA from January 2016 to December 2019. Clinical features, genetic diagnoses, and their effects on clinical interventions were collected for analysis. In the 354 enrolled patients, 131 (37%) received genetic diagnoses; 95 (72.5%) of them were autosomal recessively inherited diseases. Two hundred and fifteen variants spanning 57 genes were classified as pathogenic (P) or likely pathogenic (LP) in 131 patients. The leading cause was metabolic disorders due to 35 genes found in 89 patients (68%). The other 42 NMA patients (32%) with 22 genes had malformations and renal, neuromuscular, and immune-hematological disorders. Seven genes (MMUT, MMACHC, CHD7, NPHS1, OTC, IVD, and PHOX2B) were noted in more than four patients, accounting for 48.9% (64/131) of the identified P/LP variants. Forty-six diagnosed patients with uncorrected NMA died or gave up. In conclusion, 37% of neonates with metabolic acidosis had genetic disorders. Next-generation sequencing should be considered when investigating the etiology of NMA in NICUs. Based on early molecular diagnoses, valuable treatment options can be provided for some genetic diseases to achieve better outcomes.

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