Kiraz Aslihan, Erdogan Murat, Balta Burhan, Gumus Hakan, Mutlu Mehmet Burak, Mammadova Nurana, Ozcelik Firat, Sahin Izem Olcay, Guven Ahmet Sami, Kumandas Sefer, Savranlar Ahmet, Karaman Filiz, Per Huseyin, Dundar Munis
Department of Medical Genetics, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Department of Medical Genetics, Kayseri City Education and Research Hospital, Kayseri, Turkey.
Neurogenetics. 2025 May 31;26(1):47. doi: 10.1007/s10048-025-00825-8.
Joubert syndrome (JS) is a rare autosomal recessive genetic disease characterized by molar tooth sign, hypotonia during infancy, developmental delay, and/or intellectual disability. Over 40 genes have been associated with the syndrome, and population-specific founder variants have been defined.
In our study, we evaluated 34 patients with clinical, radiological, and laboratory findings. Whole exome sequencing (WES) analysis was performed on all patients to explain the underlying genetic causes. Optical genome mapping (OGM) was performed to elucidate the genetic mechanism in two patients with heterozygous variants after WES analysis.
Eighteen homozygous, three compound heterozygous, and two heterozygous variants were present in thirteen patients. AHI1, c.961dupG, p.Asp321fs5; CPLANE1, c.569A > G, p.Glu190Gly; CPLANE1, c.7495dup, Ile2499Asnfs2; CC2D2A, c.4143G > T, p.Lys1381Asn; KIAA0586, c.4889 T > C, p.Leu1630Pro; PIBF1, c.1231C > T, p.Arg411Ter; TMEM237, c.591delG, p.Thr198Profs*5; TMEM138, c.376G > C, p.Ala126Pro were novel variants. In addition, in the OGM analysis, a heterozygous insertion was detected in the 3'UTR region of RPGRIP1L. Patients with a diagnosis of JS that could not be explained by WES itself but could be explained together with OGM were discussed.
This study contributes to the clinical and molecular characteristics of JS patients. Despite growing literature about JS, this is the first study to use OGM for the diagnosis.
乔伯特综合征（JS）是一种罕见的常染色体隐性遗传病，其特征为磨牙征、婴儿期肌张力减退、发育迟缓及/或智力残疾。超过40个基因与该综合征相关，且已确定了特定人群的奠基者变异。
在我们的研究中，我们评估了34例具有临床、放射学和实验室检查结果的患者。对所有患者进行全外显子组测序（WES）分析以解释潜在的遗传原因。在WES分析后，对两名具有杂合变异的患者进行光学基因组图谱（OGM）分析以阐明遗传机制。
13例患者中存在18个纯合变异、3个复合杂合变异和2个杂合变异。AHI1基因，c.961dupG，p.Asp321fs5；CPLANE1基因，c.569A＞G，p.Glu190Gly；CPLANE1基因，c.7495dup，Ile2499Asnfs2；CC2D2A基因，c.4143G＞T，p.Lys1381Asn；KIAA0586基因，c.4889T＞C，p.Leu1630Pro；PIBF1基因，c.1231C＞T，p.Arg411Ter；TMEM237基因，c.591delG，p.Thr198Profs*5；TMEM138基因，c.376G＞C，p.Ala126Pro为新变异。此外，在OGM分析中，在RPGRIP1L的3'UTR区域检测到一个杂合插入。对那些无法用WES本身解释但可与OGM一起解释的JS诊断患者进行了讨论。
本研究有助于了解JS患者的临床和分子特征。尽管关于JS的文献不断增加，但这是首次使用OGM进行诊断的研究。
