The rate and significance of type 1/type 2 serum amyloid A protein gene polymorphisms in patients with ankylosing spondylitis and amyloidosis.

A relationship between the presence of amyloidosis and SAA1 genotype has been shown in recent studies of (principally) familial Mediterranean fever patients. We found that the SAA1 rs12218 polymorphism was significantly more prevalent in ankylosing spondylitis patients with amyloidosis.

Gene mutations in chronic kidney disease patients with secondary hyperparathyroidism and Sagliker syndrome.

Sagliker syndrome (SS) develops particularly before puberty while chronic kidney disease (CKD) reaches stage 3 with overt secondary hyperparathyroidism. We conducted screening for mutations in all the 13 exons of GNAS1 gene, all 3 exons of FGF23, and all 18 exons in FGFR3 genes in 23 patients. In 73.9% (17 of 23) patients, 17 genetic abnormalities in GNAS1 were detected. Seven (58.3%) of 12 nucleotide alterations comprised novel missense mutations and 3 nonsense. Mismutations were in different manner. There were also 6 heterozygous transversion polymorphisms in exons. Six were introngenic mutations (introns 65626, 70387, 70817). We found 10 mutations with different manner in FGF23 gene. Two were defined previously but remaining 8 were novel mutations. Three were in intronic region near exon 2. We sequenced all exons and intronic regions near exon-exon junction regions of FGFR3 gene. We found 22 mutations with different manner. Six were defined previously and remaining 16 were novel mutations. Eight of them were in intronic region near exon 11 and the last 2 were in noncoding exonic region of exons. One was in the exon-exon junction region between exon 11 and 12, therefore this mutation might be preventing splicing of this intron. Because the incidence of CKD late stage 3 is around 8% but the incidence of SS is around 0.5% in CKD, these gene mismutations might be responsible for bone deformities such as McCune-Albright syndrome and achondroplasias. Although our patients were not resembling any of them, they could be in between, and SS might be a combination-compulsion of bone dysplasias-hereditary osteodystrophies and CKD.

International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4.

Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS.

International study on Sagliker syndrome and uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic kidney disease patients.

OBJECTIVE: It is known that skeletal changes due to secondary hyperparathyroidism (SH) can be severe in chronic kidney disease (CKD). Recently described Sagliker syndrome (SS) is a very striking and prominent feature of SH in CKD, including an uglifying appearance to the face, short stature, extremely severe maxillary and mandibulary changes, soft tissue in the mouth, teeth/dental abnormalities, fingertip changes, knee and scapula deformities, hearing abnormalities, and neurological and, more important, severe psychological problems. DESIGN, SETTING, PATIENTS: In the past 8 years, we have encountered 40 cases of SS in SH and CKD by performing an international study in Turkey, India, Romania, Egypt, Maleysia, Tunis, and China. RESULTS: The medical history of these patients showed that they did not receive proper therapy. Changes, particularly in children and teenagers, become irreversible, which was disastrous for the patients both aesthetically and psychologically. CONCLUSION: Treatment must begin early and be the appropriate treatment given in centers with sophisticated skills. Otherwise, the inability to correct all the changes in the skull and face, to remodel a new face, to extending the height, and, most important, to convince the patients to face the dramatic psychological problems can be catastrophic for those patients.

Cephalometric evaluation of patients with Sagliker syndrome: uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic renal failure patients.

It is well known that secondary hyperparathyroidism may be an extremely severe condition in chronic renal failure, and almost all patients with chronic kidney disease, even in the well-developed countries, encounter every kind of bone abnormalities if they are not treated properly. Although some sporadic cases have been reported of unique facial bone changes, the largest collection of this phenomenon has been reported by Sagliker et al. We also have found 6 of 9 patients who have these changes (Sagliker syndrome) to manifest class II malocclusion of the upper and lower jaws according to dental universally accepted criteria by performing cephalometric studies, x-ray plain films, tomographic procedures, and drawing technology.

Neurologic manifestations in Sagliker syndrome: uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic renal failure patients.

Patients with chronic renal failure (CRF) often have signs and symptoms related to fluid and electrolyte disturbances, anemia, malnutrition, bone disease, and gastrointestinal problems. Vascular and neurologic impairment in particular remain an important source of morbidity and mortality in this vulnerable patient population. Sagliker syndrome is a novel syndrome that was recently described in 2004 in patients with CRF and severe and late secondary hyperparathyroidism who suffered from severe skull and facial bone changes, particularly from uglifying human face appearances and neuropsychiatric disorders. The goal of this study was to assess neuropsychiatric manifestations occurring in CRF patients with Sagliker syndrome. Four female and 8 male patients with CRF on regular dialysis at the hemodialysis units of the Internal Medicine Departments around southern Turkey participated in the study. All patients underwent a clinical neurologic examination performed by the same neurologist. Neuropsychiatric signs and symptoms were found in all cases. The results showed that the most frequent neurologic manifestations in CRF patients with Sagliker syndrome were headache, polyneuropathy, cranial neuropathy, fatigue, and psychiatric disorders.