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Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome
- Source :
- Clinical Neurology and Neurosurgery. 224:107560
- Publication Year :
- 2023
- Publisher :
- Elsevier BV, 2023.
-
Abstract
- © 2022 Elsevier B.V.Objective: Joubert syndrome is a neurodevelopmental disorder with a distinctive hindbrain malformation called molar tooth sign, causing motor and cognitive impairments. More than 40 genes have been associated with Joubert syndrome. We aim to describe a group of Joubert syndrome patients clinically and genetically emphasizing organ involvement. Methods: We retrospectively collected clinical information and molecular diagnosis data of 22 patients with Joubert syndrome from multiple facilities. Clinical exome or whole-exome sequencing were performed to identify causal variations in genes. Results: The most common variants were in the CPLANE1, CEP290, and TMEM67 genes, and other causative genes were AHI1, ARMC9, CEP41, CSPP1, HYLS1, KATNIP, KIAA0586, KIF7, RPGRIP1L, including some previously unreported variants in these genes. Multi-systemic organ involvement was observed in nine (40%) patients, with the eye being the most common, including Leber\"s congenital amaurosis, ptosis, and optic nerve coloboma. Portal hypertension and esophageal varices as liver and polycystic kidney disease and nephronophthisis as kidney involvement was encountered in our patients. The HYLS1 gene, which commonly causes hydrolethalus syndrome 1, was also associated with Joubert syndrome in one of our patients. A mild phenotype with hypophyseal hormone deficiencies without the classical molar tooth sign was observed with compound heterozygous and likely pathogenic variants not reported before in the KATNIP gene. Conclusion: Some rare variants that display prominent genetic heterogeneity with variable severity are first reported in our patients. In our study of 22 Joubert syndrome patients, CPLANE1 is the most affected gene, and Joubert syndrome as a ciliopathy is possible without a classical molar tooth sign, like in the KATNIP gene-affected patients.
- Subjects :
- ARMC9
SURGERY
CLINICAL NEUROLOGY
Sağlık Bilimleri
Clinical Medicine (MED)
Joubert Syndrome
KATNIP
Nöroloji (klinik)
Nöroloji
Surgery Medicine Sciences
Joubert syndrome
Health Sciences
Klinik Tıp (MED)
Molar tooth sign
Molar Tooth Sign
Cerrahi
KLİNİK NÖROLOJİ
Internal Medicine Sciences
Klinik Tıp
CERRAHİ
Dahili Tıp Bilimleri
General Medicine
CLINICAL MEDICINE
Tıp
Neurology
Cerrahi Tıp Bilimleri
Medicine
Surgery
Neurology (clinical)
HYLS1
Subjects
Details
- ISSN :
- 03038467
- Volume :
- 224
- Database :
- OpenAIRE
- Journal :
- Clinical Neurology and Neurosurgery
- Accession number :
- edsair.doi.dedup.....3f57581bf06a2db57ba2d0c85721f96c