Sinonasal polyposis is a complex chronic disease displaying contributions from multiple genetic and environmental factors. In this study, we analyzed possible genetic factors that increase susceptibility to this widespread inflammatory disease. A total of 176 adult patients, including 78 patients with sinonasal polyposis and 98 healthy controls, were analyzed for IL-1RN VNTR, IL-2(-330), and IL-4 VNTR gene polymorphisms using polymerase chain reaction and enzyme restriction. IL-1RN and IL-4 VNTR polymorphisms were notably associated with sinonasal polyposis (P = 0.0001 and P = 0.036, respectively); however, regarding the IL-2(-330) gene polymorphism, no significant difference was shown between the patient and control groups (P = 0.235). Our study indicates that the RN2 allele of IL-1RN and the RP1 allele of IL-4 might be risk factors for developing sinonasal polyposis.

This study aimed to demonstrate the diagnostic value of microarray testing in autism spectrum disorder, intellectual disability, and multiple congenital anomalies of unknown etiology, as well as to report some potential candidate genes for autism. Microarray analysis records between January 2016 and December 2017 from two Genetic Diagnostic Centers in Turkey, Kanuni Sultan Suleyman and Adana Numune Training and Research Hospital, were compiled. Detected copy number variations (CNVs) were classified as benign, likely benign, variants of uncertain significance (VUS), likely pathogenic, and pathogenic according to American College of Medical Genetics and Genomics guidelines. The clinical findings of the some patients and the literature data were compared. In 109 (24.5%) of 445 patients, a total of 163 CNVs with reporting criterion feature were detected. Sixty-nine (42%) and 8 (5%) of these were evaluated as pathogenic and likely pathogenic, respectively. Fifteen (9%) CNVs were also evaluated as VUS. Pathogenic or likely pathogenic CNVs were detected in 61 (13.6%) of 445 patients. We found that the probability of elucidating the etiology of microarray method in autism spectrum disorder, intellectual disability, and multiple congenital anomalies is 13.6% with a percentage similar to the literature. We suggest that the MYT1L, PXDN, TPO, and AUTS2 genes are all strong candidate genes for autism spectrum disorders. We detailed the clinical findings of the cases and reported that some CNV regions in the genome may be associated with autism.

Objectives: This study aims to investigate a genetic panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and examine its performance for an accurate differential diagnosis. Patients and methods: Between January 2021 and January 2022, a total of 104 children with PFAPA syndrome (63 males, 41 females; mean age: 4.8±2.3 years; range, 1.2 to 8.9 years) were retrospectively analyzed. Next-generation sequencing test was performed using a custom QIAGEN- QIAseq™ Targeted DNA Panel which includes six genes namely ELANE, LPIN2, MEFV, MVK, NLRP3, and TNFRSF1A. Results: Of 104 patients, 38 (36.5%) had variants in the genetic panel. The most common variants were found in the MEFV gene (n=35, 33.6%), the most frequent genotype was E148Q heterozygosity (n=16). Four and two patients were eventually diagnosed with Familial Mediterranean fever (FMF) and hyperimmunoglobulin D syndrome (HIDS), since they had confirmative biallelic pathogenic in the MEFV and MVK genes, respectively. Conclusion: A genetic panel, including MEFV and MVK genes, may be useful in patients, clinically resembling PFAPA, since they may have HIDS or FMF, but lack typical features of the exact disease. Nonetheless, we believe that distinct genetic panels should be developed for different populations.

The focal facial dermal dysplasias (FFDDs) are a group of rare ectodermal disorders inherited in an either autosomal dominant or an autosomal recessive pattern with characteristic facial abnormalities and bitemporal scar-like depressions resembling forceps marks (Slavotinek et al., 2013). Four subtypes of FFDDs have been reported to date. Of these, type I FFDD, or Brauer syndrome (MIM 136500), has an autosomal dominant inheritance pattern and the affected patients mostly have only the characteristic bitemporal lesions. Type II FFDD (MIM 614973), Brauer–Setleis syndrome, shows an intermediate phenotype with autosomal dominant inheritance. Type III FFDD or Setleis syndrome (SS) (MIM 227260) is a severe form of FFDD with obvious dysmorphic features in affected individuals. Finally, type IV FFDD (MIM 614974) is characterized by preauricular atrophic skin lesions. (Kowalski and Fenske, 1992). SS can have an inheritance pattern of either autosomal recessive or autosomal dominant. Characteristic facial dysmorphic features of the patients are forceps-like lesions at the temples, multiple rows of eyelashes on the upper eyelid (distichiasis), sparse lateral and upslanting eyebrows, absent meibomian glands, slanted eyebrows, wrinkled facial skin, a bulbous nose, thick protruding lips, and chin defects, which have been described as a leonine appearance (Setleis et al., 1963; Kent et al., 2007; Cervantes-Barragán et al., 2011; Giordano et al., 2014; Girisha et al., 2014). A homozygous nonsense mutation was reported in the TWIST2 gene, encoding a member of the basic helix–loop–helix protein (bHLH) family, a transcriptional regulatory protein functioning in mesenchymal cell lineage differentiation (Tukel et al., 2010). In 2013, a CYP26C1 gene mutation was reported as a cause of FFDD type IV by (Slavotinek et al., 2013). In addition, duplications of chromosome 1p36 have been reported as a cause in FFDD and SS without the presence of a TWIST2 mutation (Weaver et al., 2015). Here, we report a patient clinically and molecularly diagnosed with SS and mild dysmorphic features of heterozygous mutated cases in heterozygotes in his family. The proband (Fig. 1), a 13-year-old male, was referred to our clinical genetics department because of his coarse facial appearance. He was born to a consanguineous couple (first cousins) at full term and the delivery was spontaneous with no forceps-use after a noncomplicated pregnancy. Medical records of his birth weight, length, and head circumference were not available. His current growth parameters were within the normal ranges. On examination at the age of 13 years, he had a coarse facial appearance with sparse lateral eyebrows and eyelashes, temporal forceps signs, high-arched eyebrows, periorbital puffiness, downslanting palpebral fissures, prominent nasal bridge, low frontal hairline, and a vertical groove below the lower lip. His voice was high pitched and he had poor vocalization. His mental development was evaluated as normal. He had psychological problems attributed to his dysmorphic facial appearance. In terms of family history, he had two brothers and a sister. One of the brothers, later shown to have a heterozygous mutation, had mild dysmorphic facial features including a prominent chin, and sparse eyelashes and eyebrows. His mother and father had similar mild dysmorphic features. DNA was extracted from EDTA-peripheral blood samples using a commercial kit according to the instructions of the manufacturer (Invitrogen, Carlsbad, California, USA). Primers were designed for amplification of exon 1 and 2 of the TWIST2 gene. PCR products were analyzed upon electrophoresis in 2% agarose gels. Purified gene-specific amplicons from PCR were sequenced by capillary electrophoresis in an ABI 3130 genetic analyzer (Applied BioSystems, Foster City, California, USA).