Molecular Evaluation of Joubert Syndrome and Hearing Impairment in a Patient with Ataxic Cerebral Palsy

Abstract

Joubert syndrome (JBTS) is a rare autosomal recessive or X-linked congenital brain malformation with strong genetic heterogeneity. Other neurological features of JBTS include hypotonia, ataxia, developmental delay, and cognitive impairment. Hearing loss with JBTS has been reported in the literature. We present the case of a 3.5-year-old boy born to a healthy consanguineous South Indian couple who was presented with ataxic cerebral palsy (CP) and hearing impairment; medical reports confirmed typical brain malformations of JBTS. Hearing impairment was screened by audiological assessment, which confirmed the presence of severe-profound hearing loss with outer hair cell dysfunction. Whole-exome sequencing (WES) was performed to know the molecular aspects of the condition and to detect any novel mutations. The homozygous mutation AHI1 c.2023G > A associated with JBTS type 3 and GJB2 c.71G > A mutation associated with hearing impairment were identified. Sanger sequencing was performed to validate the result and it identified heterozygous AHI1 c.2023G > A and GJB2 c.71G > A in the patient's parents. This study confirms the diagnosis of JBTS by WES helps identify the genetic causes of hereditary disorders that accelerate genetic evaluation and counseling for at-risk families.

Keywords

Joubert syndrome - hearing loss - AHI1 - GJB2

Ethical Approval

The study was approved by the Ethics Committee of All India Institute of Speech and Hearing, Mysore, India.

Author Contribution

N. Sreedevi was responsible for conceptualization, supervision, and project administration. N Swapna contributed to conceptualization. Santosh Maruthy was responsible for supervision and project administration. T. Jayakumar contributed to supervision. Charles Sylvester was responsible for the methodology, molecular biology, bioinformatics, and writing the original manuscript.

Publication History

Received: 12 May 2023

Accepted: 20 June 2023

Article published online:
17 July 2023

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