Genomic Testing for Diagnosis of Genetic Disorders in Children: Chromosomal Microarray and Next—Generation Sequencing

2020 ◽  
Vol 57 (6) ◽  
pp. 549-554
Author(s):  
Dhanya Lakshmi Narayanan ◽  
Katta Mohan Girisha
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Disorders ◽  
Chromosomal Microarray ◽  
Genomic Testing ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Clinical and neuroimaging phenotypes of genetic parkinsonism from infancy to adolescence

Brain ◽  
2019 ◽  
Vol 143 (3) ◽  
pp. 751-770 ◽  
Author(s):  
Hugo Morales-Briceño ◽  
Shekeeb S Mohammad ◽  
Bart Post ◽  
Alessandro F Fois ◽  
Russell C Dale ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Movement Disorders ◽  
Early Onset ◽  
Genetic Disorders ◽  
Phenotypic Characterization ◽  
Imaging Features ◽  
Next Generation ◽  
Phenotypic Spectrum ◽  
Inherited Mutations ◽  
Generation Sequencing

Abstract Genetic early-onset parkinsonism presenting from infancy to adolescence (≤21 years old) is a clinically diverse syndrome often combined with other hyperkinetic movement disorders, neurological and imaging abnormalities. The syndrome is genetically heterogeneous, with many causative genes already known. With the increased use of next-generation sequencing in clinical practice, there have been novel and unexpected insights into phenotype-genotype correlations and the discovery of new disease-causing genes. It is now recognized that mutations in a single gene can give rise to a broad phenotypic spectrum and that, conversely different genetic disorders can manifest with a similar phenotype. Accurate phenotypic characterization remains an essential step in interpreting genetic findings in undiagnosed patients. However, in the past decade, there has been a marked expansion in knowledge about the number of both disease-causing genes and phenotypic spectrum of early-onset cases. Detailed knowledge of genetic disorders and their clinical expression is required for rational planning of genetic and molecular testing, as well as correct interpretation of next-generation sequencing results. In this review we examine the relevant literature of genetic parkinsonism with ≤21 years onset, extracting data on associated movement disorders as well as other neurological and imaging features, to delineate syndromic patterns associated with early-onset parkinsonism. Excluding PRKN (parkin) mutations, >90% of the presenting phenotypes have a complex or atypical presentation, with dystonia, abnormal cognition, pyramidal signs, neuropsychiatric disorders, abnormal imaging and abnormal eye movements being the most common features. Furthermore, several imaging features and extraneurological manifestations are relatively specific for certain disorders and are important diagnostic clues. From the currently available literature, the most commonly implicated causes of early-onset parkinsonism have been elucidated but diagnosis is still challenging in many cases. Mutations in ∼70 different genes have been associated with early-onset parkinsonism or may feature parkinsonism as part of their phenotypic spectrum. Most of the cases are caused by recessively inherited mutations, followed by dominant and X-linked mutations, and rarely by mitochondrially inherited mutations. In infantile-onset parkinsonism, the phenotype of hypokinetic-rigid syndrome is most commonly caused by disorders of monoamine synthesis. In childhood and juvenile-onset cases, common genotypes include PRKN, HTT, ATP13A2, ATP1A3, FBX07, PINK1 and PLA2G6 mutations. Moreover, Wilson’s disease and mutations in the manganese transporter are potentially treatable conditions and should always be considered in the differential diagnosis in any patient with early-onset parkinsonism.

scholarly journals Current use of chromosomal microarray by Australian paediatricians and implications for the implementation of next generation sequencing

2017 ◽  
Vol 53 (7) ◽  
pp. 650-656 ◽  
Author(s):  
Victoria McKay ◽  
Daryl Efron ◽  
Elizabeth E Palmer ◽  
Susan M White ◽  
Chris Pearson ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Chromosomal Microarray ◽  
Next Generation ◽  
Generation Sequencing

Next-Generation Sequencing to Diagnose Suspected Genetic Disorders

2018 ◽  
Vol 379 (14) ◽  
pp. 1353-1362 ◽  
Author(s):  
David R. Adams ◽  
Christine M. Eng
Keyword(s):  
Next Generation Sequencing ◽  
Genetic Disorders ◽  
Next Generation ◽  
Generation Sequencing

Utilization of next generation sequencing to characterize duplications identified through chromosomal microarray

2021 ◽  
Vol 132 ◽  
pp. S284
Author(s):  
John Herriges ◽  
Isabelle Thiffault ◽  
Joseph T. Alaimo ◽  
Florencia del Viso ◽  
Holly Welsh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Chromosomal Microarray ◽  
Next Generation ◽  
Generation Sequencing
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