Kindler syndrome (OMIM 173650) is an autosomal recessive genodermatosis characterized by trauma-induced blistering, poikiloderma, skin atrophy, mucosal inflammation and varying degrees of photosensitivity. Although Kindler syndrome is classified as a subtype of epidermolysis bullosa, it has distinct clinicopathological and molecular abnormalities. The molecular pathology of Kindler syndrome involves loss-of-function mutations in a newly recognized actin cytoskeleton-associated protein, now known as fermitin family homologue 1, encoded by the gene FERMT1. This protein mediates anchorage between the actin cytoskeleton and the extracellular matrix via focal adhesions, and thus the structural pathology differs from other forms of epidermolysis bullosa in which there is a disruption of the keratin intermediate filament-hemidesmosome network and the extracellular matrix. In the skin, fermitin family homologue 1 is mainly expressed in basal keratinocytes and binds to the cytoplasmic tails of beta1 and beta3 integrins as well as to fermitin family homologue 2 and filamin-binding LIM protein 1. It also plays a crucial role in keratinocyte migration, proliferation and adhesion. In this report, we review the clinical, cellular and molecular pathology of Kindler syndrome and discuss the role of fermitin family homologue 1 in keratinocyte biology.

Alström Syndrome 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. Alström Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to play 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 Alström Syndrome. 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, there 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 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, 8 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 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. Additionally, 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. Alström Syndrome 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 Alström Syndrome and contribute to genotype-phenotype correlation studies.

Both decreased amplitude and prolonged latency of P300 are associated with IR in children with obesity, which shows the impairment of neural activity associated with sensory and cognitive information processing in these children. Further studies are necessary to strengthen the current findings and to determine the exact mechanism of cognitive impairment in obese children.

Diameters of thoracic vascular structures increase with age. The consistent vertebral to vessel ratios can be useful in evaluation of chest CT of pediatric patients.

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Alström Syndrome is a clinically complex disorder characterized by childhood retinal degeneration leading to blindness, sensorineural hearing loss, obesity, type 2 diabetes mellitus, cardiomyopathy, systemic fibrosis, and pulmonary, hepatic, and renal failure. Alström Syndrome is caused by recessively inherited mutations in the ALMS1 gene, which codes for a putative ciliary protein. Alström Syndrome is characterized by extensive allelic heterogeneity, however founder effects have been observed in some populations. To date, more than 100 causative ALMS1 mutations have been identified, mostly frameshift and nonsense alterations resulting in termination signals in ALMS1. Here we report a complex Turkish kindred in which sequence analysis uncovered an insertion of a novel 333 basepair Alu Ya5 SINE retrotransposon in the ALMS1 coding sequence, a previously unrecognized mechanism underlying mutations causing Alström Syndrome. It is extraordinarily rare to encounter the insertion of an Alu retrotransposon in the coding sequence of a gene. The high frequency of the mutant ALMS1 allele in this isolated population suggests that this recent retrotransposition event spread quickly, and may be used as a model to study the population dynamics of deleterious alleles in isolated communities.

A 1-year-old boy with epistaxis, gastrointestinal bleeding and severe anemia that caused cardiorespiratory distress presented to our unit. The results of coagulation tests were normal. An erythrocyte suspension transfusion was given to the patient. On the second day of his hospitalization, a leech was removed from his nose. In developing countries, leech infestation should be considered in cases where epistaxis, hematemesis, gastrointestinal bleeding and severe anemia are of unknown origin.

This study aims to compare neurological examination and cranial magnetic resonance imaging (MRI) findings in patients with serious hyperbilirubinemia. Twenty-one serious hyperbiluribinemic term neonates (6 girls, 15 boys) who underwent exchange transfusions were included in the study. Neurological examination findings, body weight, age at admission, blood culture, urine culture, urine analysis, C-reactive protein, thyroxine, thyroid-stimulating hormone, total and indirect bilirubin levels, causes of hyperbilirubinemia (blood group typing, glucose-6-phosphate dehydrogenase, blood smear, tandem mass), treatment and duration of follow-up, auditory test results, and cranial MRI findings were evaluated. All patients were term neonates with an average body weight of 2943 +/- 533 g. The mean age at admission was 4.47 +/- 2.22 days, and the mean bilirubin level was 35.0 +/- 10.8 mg/dL. Exchange transfusion was performed once in all, except 4 patients who needed 2 transfusions. Kernicterus findings were found in 76% of patients on neurological examination, and cranial MRI detected a pathological finding in 71% of patients. In 2 patients, cranial MRI showed kernicterus findings, despite normal neurological examination. In contrast, in 3 patients, despite kernicterus findings in neurological examination, cranial MRI was normal. Although cranial MRI has an important place in the diagnosis of kernicterus, it does not always correlate with clinical findings. We believe that studies with larger series are warranted.