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

Jing Zhang; Lihui Wang; Wenqi Chen; Jun Duan; Yanxin Meng; Huafang Yang; Qing Guo

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

Am J Transl Res. 2022 Jul 15;14(7):5088-5097. eCollection 2022.

Authors

Jing Zhang¹, Lihui Wang², Wenqi Chen¹, Jun Duan³, Yanxin Meng¹, Huafang Yang², Qing Guo¹

Affiliations

¹ Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital, Hebei Medical University (Key Laboratory of Maternal and Fetal Medicine of Hebei Province) Shijiazhuang, Hebei, China.
² Neurology Department, Children's Hospital of Hebei Province, Hebei Medical University Shijiazhuang, Hebei, China.
³ Radiology Department, Shijiazhuang Obstetrics and Gynecology Hospital, Hebei Medical University Shijiazhuang, Hebei, China.

PMID: 35958498
PMCID: PMC9360900

Abstract

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.

Keywords: AHI1; C5orf42; CC2D2A; Joubert syndrome; NPHP1.