Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome

© 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

On the Stationary Distribution for a Fuzzy Inventory Model of Type (s,S) with Inverse Gaussian Distributed Demands

In this study, we consider a fuzzy inventory model of type (s,S) with random demands having an inverse Gaussian distribution. We first show the monotonicity of the renewal function with respect to mean parameter. Thus we obtain the membership function of the fuzzy renewal function when the amount of demands is a random variable having an inverse Gaussian distribution with a fuzzy mean parameter by using the monotonicity property of renewal function. Making use of the membership function of the renewal function, we obtain the membership function of the fuzzy ergodic distribution of this process. We also present some numerical results obtained by using this membership function.[Khaniyev, Tahir; Turksen, I. Burhan] TOBB Univ Econ & Technol, Dept Ind Engn, TR-06560 Ankara, Turkey; [Khaniyev, Tahir] Natl Acad Sci Azerbaijan, Inst Cybernet, AZ-1141 Baku, Azerbaijan; [Gokpinar, Fikri] Gazi Univ, Dept Stat, TR-06500 Ankara, Turkey; [Hanalioglu, Tagi] Bogazici Univ, Dept Ind Engn, Istanbul, Turkey; [Turksen, I. Burhan] Univ Toronto, Dept Mech & Ind Engn, Toronto, ON M5S 3G8, Canad