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WOS: 000348684000001, PubMed ID: 25296579, Alstrom syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alstrom Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alstrom Syndrome and contribute to genotype-phenotype correlation studies., NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [HD036878]; DPTTurkiye Cumhuriyeti Kalkinma Bakanligi [1206400603]; TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [111S217]; TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK), We are grateful to Alstrom Syndrome International and Nevin Bengur, Alstrom Syndrome-Canada, Alstrom Sendromu Dernegi Turkey. We are grateful to A Dufke, A Kiraz, F Silan, H Onal, JR Lupski, N Narin, O Cogulu, S Gunis-Bilgili, S Tasdemir, T Ucar, Y Seckin, and many physicians who referred their patients for this study. This study was supported, in part, by NIH HD036878 (JKN, JDM, GBC), DPT 1206400603 and TUBITAK, 111S217, Turkey (AO and RKO).

We report a 6 year-old boy with the simple virilizing form of 21-hydroxylase deficiency in whom an adrenal adenoma developed following 5 years of steroid treatment. Extremely high levels of basal serum 17alpha-hydroxyprogesterone as well as an exaggerated response of 17alpha-hydroxyprogesterone to adrenocorticotropic hormone confirmed congenital adrenal hyperplasia at 7 years of age. Initially elevated serum steroid levels were restrained by high dose hydrocortisone therapy, but he chronically tended to take inadequate doses of glucocorticoid. At 12 years of age an adenoma was found in the cortex of the hyperplastic right adrenal gland. The importance of early diagnosis and compliance with medication in the simple virilizilng form of 21-hydroxylase deficiency is stressed.