Background and objective Primary ciliary dyskinesia (PCD) is a rare and genetically heterogeneous disease and the severity of the disease related with genetic analysis has been described in some previous studies. The main aim of our study was to describe the clinical characteristics and laboratory findings of patients with genetically diagnosed PCD and to investigate the correlation between clinical, radiologic, and laboratory findings and genetic analyses of these patients. Method This is a cohort study in which we analyzed the clinical characteristics, laboratory findings, and genetic results of 46 patients with genetically diagnosed PCD through whole‐exome sequencing at our single center from a total of 265 patients with PCD within a 5‐year period. Results Genetic analysis revealed pathogenic variants in DNAH5 (n = 12 individuals, 12 families), CCDC40 (n = 9 individuals, six families), RSPH4A (n = 5 individuals, three families), DNAH11 (n = 4 individuals, four families), HYDIN (n = 5 individuals, five families), CCNO (n = 4 individuals, four families), DNAI1 (n = 2 individuals, one family), ARMC4 (n = 2 individuals, two families), TTC25 (n = 1), DNAH1 (n = 1), and CCDC39 (n = 1) genes. Although not statistically significant, the age at diagnosis was lower (median: 3 years; range, 6 months‐4 years) in patients with CCNO pathogenic variants due to the early reporting of symptoms, and the median body mass index (BMI) and BMI z scores were lower in patients at 18.7 and 16 kg/m2, and −0.78 and −1.2 with CCDC40 and CCNO pathogenic variants, respectively. The median forced expiratory flow in 1 second (FEV1%), forced vital capacity (FVC%), and forced expiratory flow (FEF)25‐75% were 53%, 64%, and 28%, respectively; these parameters were also lower in the CCDC40 group than in the other groups. There was no significant correlation between the genetic results and symptoms, radiologic findings, and microbiologic data of patients with PCD. Conclusion In PCD, there was significant heterogeneity of lung disease, patients who had pathogenic variants in CCNO presented earlier, and those with CCDC40 and CCNO had worse lung disease, and poorer nutritional status compared with the other subgroups. We hope that whole genotype‐phenotype and clinical relationships will be identified in PCD.

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Nephronophthisis (NPHP) is one of the most common genetic causes of CKD; however, the underlying genetic abnormalities have been established in ,50% of patients. We performed genome-wide analysis followed by targeted resequencing in a Turkish consanguineous multiplex family and identified a canonic splice site mutation in ANKS6 associated with an NPHP-like phenotype. Furthermore, we identified four additional ANKS6 variants in a cohort of 56 unrelated patients diagnosed with CKD due to nephronophthisis, chronic GN, interstitial nephritis, or unknown etiology. Immunohistochemistry in human embryonic kidney tissue demonstrated that the expression patterns of ANKS6 change substantially during development. Furthermore, we detected increased levels of both total and active b-catenin in precystic tubuli in Han:SPRD Cy/+ rats. Overall, these data indicate the importance of ANKS6 in human kidney development and suggest a mechanism by which mutations in ANKS6 may contribute to an NPHP-like phenotype in humans.

Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Other findings included bilateral partial cutaneous syndactyly of 2nd and 3rd fingers, history of impacted teeth with dentigerous cyst in the elder one, and intellectual disability (mild and borderline). The sisters were considered to have Elsahy-Waters syndrome. In order to elucidate the underlying molecular cause, sisters and their healthy parents were genotyped by SNP arrays, followed by homozygosity mapping. Homozygous regions were further analyzed by exome sequencing in one affected individual. A homozygous indel variant segregating with the condition was detected in CDH11 (c.1116_1117delinsGATCATCAG, p.(Ile372MetfsTer9)), which was then validated by using Sanger sequencing. CDH11 encodes cadherin 11 (osteo-cadherin) that regulates cell-cell adhesion, cell polarization and migration, as well as osteogenic differentiation. Further experiments revealed that CDH11 expression was decreased in patient-derived fibroblasts as compared to the heterozygous parent and another healthy donor. Immunostaining showed absence of the protein expression in patient fibroblasts. In addition, cell proliferation rate was slow and osteogenic differentiation potential was delayed. We consider that this study reveals loss-of-function mutations in CDH11 as a probable cause of this phenotype. Next generation sequencing in further patients would both prove this gene as causative, and finely delineate this clinical spectrum further contributing in identification of other possibly involved gene(s).

Five patients had homozygous alterations in genes coding early complement proteins. This may lead to decreased clearance of apoptotic bodies. One patient had variant, which functions in the clearance of self-antigens. In 1 patient, we determined a novel gene that may be important in SLE pathogenesis. We suggest that monogenic causes/associations should be sought in early-onset and/or familial SLE.

IntroductionStudies on different life history trait strategies under stressful environments are crucial in understanding how evolution shapes an organism under extreme conditions (Roff, 1992;Stearns, 1992;Flatt, 2011). Effects of dietary restriction (DR) as an environmental stress on life history traits have been assessed over the past 80 years, since the first positive correlation shown by McCay et al. (1935) between DR and median life span. Nutritional manipulation is one of the most frequently used ways to expose the effects of food as an environmental variable on the life history traits of organisms (Onder and Yilmaz, 2009). Subsequent studies with model organisms have indicated that life history traits change with respect to decreasing food medium (Mair, 2005;Speakman and Sharon, 2011).The amount and quality of nutrients consumed by organisms have a particular impact on life history traits, including developmental time, body size, and survival. Exposure to stress during developmental periods is significant for all organisms, especially for holometabol insects; moreover, instability in developmental periods can affect many adult characters. A nutrition intake decrease in the developmental stage extends developmental time and reduces adult body and organ size (Shingleton et al., 2008). Roff modeled the interaction between growth, developmental time, and body size in 2000 (Roff, 2000). Depending on the model, all variables have close relations with each other and are also affected by environmental stress. Variations in the quantity or quality of an acceptable diet can have profound effects on insect development (Chapman, 1998).Developmental stage stability is highly related to an organism's fitness, which critically depends on growth and development, as in the model of Roff (2000). However,

Inherited CD59 deficiency is a rare autosomal recessive disorder characterized by chronic hemolysis, recurrent ischemic central nervous system strokes, and early-onset relapsing peripheral demyelinating neuropathy mimicking recurrent Guillain–Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP). We report a 7-year-old girl who presented with neonatal-onset relapsing weakness accompanied by diffuse sensory-motor demyelinating peripheral polyneuropathy. She was diagnosed as having a CIDP-like disease and partially responded to immunomodulatory treatments. Cranial magnetic resonance imaging showed multiphasic brainstem and cerebellar ischemic lesions consistent with vasculopathy and chronic left middle cerebral artery infarction. Whole exome sequencing (WES) analysis revealed a frameshift deletion in CD59 (c.146delA, p.Asp49Valfs*31). Inherited CD59 deficiency should be considered in the differential diagnosis of patients with early-onset severe neurologic symptoms even without an overt hemolysis. We would like to highlight the role of WES in the diagnosis of a condition with a targeted therapy.

Colony stimulating factor 1 receptor (CSF1R, MIM# 164770) encodes a tyrosine‐kinase receptor playing an important role in development of osteoclasts and microglia. Heterozygous CSF1R variants have been known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS, MIM# 221820), an adult‐onset leukoencephalopathy characterized by loss of motor functions and cognitive decline. Recently, a new phenotype characterized by brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) with biallelic CSF1R pathogenic variants in the etiology has been described. BANDDOS differs from HDLS by early‐onset neurodegenerative changes with additional structural brain abnormalities and skeletal findings resembling dysosteosclerosis (DOS). Described skeletal findings of the disease are highly variable ranging from absence of a skeletal phenotype and milder Pyle disease‐like to osteopetrosis and DOS. To date, only a few patients carrying biallelic CSF1R variants have been reported. In this clinical report, we describe three siblings with variable skeletal findings along with neurological symptoms ranging from mild to severe in whom exome sequencing revealed a novel homozygous splice site variant in canonical splice donor site of intron 21 adjacent to an exon, which encoding part of kinase domain of CSF1R along with a review of the literature.