Four mutations in MITF, SOX10 and PAX3 genes were identified as genetic causes of waardenburg syndrome in four unrelated Iranian patients: case report.

BACKGROUND: Waardenburg syndrome (WS) is a rare genetic disorder. The purpose of this study was to investigate clinical and molecular characteristics of WS in four probands from four different Iranian families. CASE PRESENTATION: The first patient was a 1-year-old symptomatic boy with congenital hearing loss and heterochromia iridis with a blue segment in his left iris. The second case was a 1.5-year-old symptomatic girl who manifested congenital profound hearing loss, brilliant blue eyes, and skin hypopigmentation on the abdominal region at birth time. The third patient was an 8-month-old symptomatic boy with developmental delay, mild atrophy, hypotonia, brilliant blue eyes, skin hypopigmentation on her hand and foot, Hirschsprung disease, and congenital profound hearing loss; the fourth patient was a 4-year-old symptomatic boy who showed dystopia canthorum, broad nasal root, synophrys, skin hypopigmentation on her hand and abdomen, brilliant blue eyes, and congenital profound hearing loss. Whole exome sequencing (WES) was used for each proband to identify the underlying genetic factor. Sanger sequencing was performed for validation of the identified mutations in probands and the available family members. A novel heterozygous frameshift mutation, c.996delT (p.K334Sfs*15), on exon 8 of the MITF gene was identified in the patient of the first family diagnosed with WS2A. Two novel de novo heterozygous mutations including a missense mutation, c.950G > A (p.R317K), on exon 8 of the MITF gene, and a frameshift mutation, c.684delC (p.E229Sfs*57), on the exon 3 of the SOX10 gene were detected in patients of the second and third families with WS2A and PCWH (Peripheral demyelinating neuropathy, Central dysmyelinating leukodystrophy, Waardenburg syndrome, Hirschsprung disease), respectively. A previously reported heterozygous frameshift mutation, c.1024_1040del AGCACGATTCCTTCCAA, (p.S342Pfs*62), on exon 7 of the PAX3 gene was identified in the patient of the fourth family with WS1. CONCLUSIONS: An exact description of the mutations responsible for WS provides useful information to explain the molecular cause of clinical features of WS and contributes to better genetic counseling of WS patients and their families.

Correlation of interleukin-6-174 GC and interleukin-6-572 GC gene polymorphisms with periodontal disease in an Iranian population.

BACKGROUND: Periodontal disease has a multifactorial etiology. A combination of microbial agents and environmental, habitual, systemic, and genetic risk factors is responsible for the development of periodontal disease. Host immune response causes the destruction of tooth-supporting structure and eventual tooth loss. This study aimed to assess the correlation of interleukin 6 (IL-6) -174-GC and IL-6-572-GC gene polymorphisms with periodontal disease in an Iranian population. MATERIALS AND METHODS: This case-control analytical study was conducted on 129 subjects presenting to the laboratory of Taleghani Hospital. Subjects underwent clinical and periodontal examinations and divided into five groups of healthy, gingivitis and mild, moderate and severe periodontitis. Blood samples (2 ml) were obtained. Genomic DNA was extracted manually using the salting-out method. IL-6 sequence amplification was performed using polymerase chain reaction with three thermal protocols. Digested products were analyzed by electrophoresis through 2% agarose gel using Gel Red staining. Data were analyzed using Chi-square, Kruskal-Wallis, and Mann-Whitney tests, and P < 0.05 was considered significant. RESULTS: The frequency of GG polymorphism at IL-6-174 and IL-6-572 genomic regions was 51.2% and 71.3%, respectively. The frequency of IL-6-572-GG polymorphism was significantly greater than that of IL-6-572-GC polymorphism (P < 0.001). Comparison of the mean and maximum pocket depth and clinical attachment level, as well as bleeding on probing percentage, revealed significant differences between the healthy controls and periodontitis patients (P < 0.001). The frequency percentages of GC and GG polymorphisms were almost equal in the healthy, gingivitis, and periodontitis groups. In other words, the frequency of the two polymorphisms was not significantly different between the health and disease states (P = 0.065 for IL-6-572 and P = 0.63 for IL-6-174). CONCLUSION: This study found no association between IL-6-174 and IL-6-572 gene polymorphisms and periodontitis in the studied population.