Whole exome sequencing facilitated the diagnosis in four Chinese pediatric cases of Joubert syndrome related disorders.

Objectives: Joubert syndrome is a spectrum of rare genetic disorders, mainly characterized by a distinctive cerebellar and brain stem malformation called the "molar tooth sign" (MTS), hypotonia, and intellectual disability/developmental delay.
Methods: In this study, 4 pediatric cases with developmental delay and oculomotor abnormities were recruited, and submitted to a clinical evaluation and magnetic resonance imaging (MRI) examination. Afterwards, genetic detection with whole exome sequencing (WES) was conducted on the 4 patients.
Results: Imaging results demonstrated cerebellar dysplasia in all probands, yet the MTS findings varied in severity. WES detected diagnostic variations in all four probands, which were distributed in four genes, namely CC2D2A, NPHP1, AHI1 , and C5orf42 . Two variants were novelly identified, which were the CC2D2A : c.2444delC (p.P815fs*2) and the AIH1 : exon (15-17) del. In silico analysis supported the pathogenicity of the variations in this study.
Conclusions: Our findings expanded the mutation spectrum of Joubert syndrome related disorders, and provided solid evidence to the affected families for further genetic counseling and pregnancy guidance.
Competing Interests: None.
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