Sreedevi N, Swapna N, Maruthy Santosh, Jayakumar T, Sylvester Charles
Department of Speech-Language Sciences, All India Institute of Speech and Hearing, Mysore, India.
Department of Speech-Language Pathology, All India Institute of Speech and Hearing, Mysore, India.
Glob Med Genet. 2023 Jul 17;10(3):190-193. doi: 10.1055/s-0043-1771184. eCollection 2023 Sep.
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 c.2023G > A associated with JBTS type 3 and c.71G > A mutation associated with hearing impairment were identified. Sanger sequencing was performed to validate the result and it identified heterozygous c.2023G > A and 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.
乔伯特综合征（JBTS）是一种罕见的常染色体隐性或X连锁先天性脑畸形，具有很强的遗传异质性。JBTS的其他神经学特征包括肌张力减退、共济失调、发育迟缓以及认知障碍。文献中已有关于JBTS伴听力损失的报道。我们报告了一例3.5岁男孩的病例，该男孩由一对健康的南印度近亲夫妇所生，患有共济失调型脑性瘫痪（CP）和听力障碍；医学报告证实其具有典型的JBTS脑畸形。通过听力学评估筛查听力障碍，结果证实存在伴有外毛细胞功能障碍的重度至极重度听力损失。进行全外显子组测序（WES）以了解该病症的分子特征并检测任何新的突变。鉴定出与3型JBTS相关的纯合突变c.2023G＞A以及与听力障碍相关的c.71G＞A突变。进行桑格测序以验证结果，结果在患者父母中鉴定出杂合的c.2023G＞A和c.71G＞A。本研究通过WES确诊JBTS，有助于确定遗传性疾病的遗传原因，从而加速对高危家庭的遗传评估和咨询。
