Ann Pediatr Endocrinol Metab.  2017 Jun;22(2):90-94. 10.6065/apem.2017.22.2.90.

Next generation sequencing and array-based comparative genomic hybridization for molecular diagnosis of pediatric endocrine disorders

• Fukami M
• Miyado M

• KMID: 2383902
• DOI: http://doi.org/10.6065/apem.2017.22.2.90

Abstract

Next-generation sequencing (NGS) and array-based comparative genomic hybridization (array CGH) have enabled us to perform high-throughput mutation screening and genome-wide copy number analysis, respectively. These methods can be used for molecular diagnosis of pediatric endocrine disorders. NGS has determined the frequency and phenotypic variation of mutations in several disease-associated genes. Furthermore, whole exome analysis using NGS has successfully identified several novel causative genes for endocrine disorders. Array CGH is currently used as the standard procedure for molecular cytogenetic analysis. Array CGH can detect various submicroscopic genomic rearrangements involving exons or enhancers of disease-associated genes. This review introduces some examples of the use of NGS and array CGH for the molecular diagnosis of pediatric endocrine disorders.

Keyword

Next-generation sequencer; Mutation; Comparative genomic hybridization; DNA Copy-number variations; Diagnosis

MeSH Terms

Comparative Genomic Hybridization*
Cytogenetic Analysis
Diagnosis*
Exome
Exons
Mass Screening

Figure

• 

  Fig. 1 Representative results of next generation sequencing. Each gray bar denotes a 100-bp DNA fragment obtained from a patient's sample. Substituted nucleotides are highlighted by colored letters. This patient carries a heterozygous A to C substitution (the blue box). All other substitutions in this figure are likely to be sequence errors.

• 

  Fig. 2 Representative results of array-based comparative genomic hybridization. Submicroscopic deletion identified in a patient with 46,XY disorders of sex development is shown. This deletion likely encompasses a cis-acting enhancer(s) of SOX914). The deletion was shared by the patient's mother. The black, red, and green dots denote signals indicative of the normal, the increased (>+0.5) and the decreased (<−1.0) copy-numbers, respectively. Green arrows depict deleted regions. Genomic positions refer to the Human Genome (hg19, build 37).

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