MECP2 mutations in Serbian Rett syndrome patients.

BACKGROUND: Rett syndrome is a severe neurodevelopmental X-linked dominant disorder affecting 1/15,000 girls worldwide. Eight years ago, the MECP2 gene was associated with the devastating clinical features observed in Rett syndrome patients. OBJECTIVES: To investigate the spectrum and the frequency of MECP2 mutations in Serbian Rett syndrome patients. PATIENTS AND METHODS: We screened the MECP2 coding region by conventional mutational screening (single-strand conformation polymorphism/sequencing) in 24 patients of Serbian origin and in their 41 unaffected family members. In search for gene dosage alterations in seemingly mutation-negative girls, we developed a new, specific quantitative PCR method. RESULTS: Nineteen patients (79%) carried MECP2 mutations, five of which were novel (one nonsense mutation, one duplication and three deletions). Fourteen previously described disease-causing sequence changes and one polymorphism were also detected. Detailed case reports are given for the carriers of the novel mutations. Large MECP2 rearrangements cause Rett syndrome in a significant number of girls without 'classic' mutations in this gene. Therefore, we developed a specific quantitative PCR method, covering MECP2 exons 3 and 4, which previously has not been used for screening. No dosage alterations of the two exons were found in the four tested mutation-negative girls. CONCLUSIONS: This is the first genetic study of Rett syndrome in Serbian patients describing the MECP2 mutational and phenotypic spectrum in this population. Detailed clinical descriptions of this ethnically homogeneous patient population add to our knowledge of genotype/phenotype correlations in this severe condition.

[Diffuse and binodular goiter in a patient with tuberous sclerosis]. / Difuzna i binodozna struma kod bolesnice sa tuberoznom sklerozom.

Tuberous sclerosis complex is hereditary multisystemic, neurocutaneous disorder characterized by hamartomatous lesions mainly involving the brain, skin and viscera. Thyroid gland is rarely affected in these patients. Case history of a patient with tuberous sclerosis complex and diffuse and binodular goiter was presented. No epileptic seizures occurred despite multiple intracranial calcifications, cortical and subependimal tubers, revealed by neuroimaging. Borderline intellectual functioning was determined. Ultrasonographic findings of the heart, abdomen and pelvis were normal. Bone radiographs revealed multiple cystic lesions of the metacarpal, metatarsal and terminal phalanges. Clinical, endocrine and metabolic evaluations were performed because of anxiety, mild weight loss, transient problems of swallowing and breathing complaints, developing when she was 39 years old. Palpable diffuse and asymmetric thyroid enlargement was found. Laboratory tests of thyroid function, ultrasonographic examination and scintiscanning of the thyroid gland and patohistological analysis of fine-needle aspiration biopsy revealed the euthyroid, inactive, diffuse and binodular goiter. Unusual association of goiter and tuberous sclerosis was discussed.

[Miraculous recoveries in the frescoes of the Decani Monastery]. / Cudesna isceljenja u zivopisu manastira decani.

Serbian medieval medicine can be said to have the same characteristics as western medicine of those times in terms of practical medical science, whereas the ancillary medical branches were under Byzantine influence. Besides the compositions of Christ's miracles and paraboles are underlying part of the fresco/painting, the scenes of Christ's miraculous recoveries have an important place in the christian iconography of the New Testament events. One of the most impressive cycles of Christ's miracles in the Serbian and Byzantine medieval art was painted in c. 1340 year in the church dedicated to the Ascension of Lord Christ at Dechani Monastery and constructed between 1327 and 1335. A considerable number of 22 frescoes of different artistic value and technique displays the miraculous recovery of patients afflicted by various chronic ailments: paralytics (razlabljeni), lepers, and handicapped (blind, lame and deaf). One scene presents the bleeding (krvotociva) women. Scenes of recovery from nervous and mental diseases are especially impressive. Patients with atrophic arm, these with hemiplegy, epilepsy, an somnambulist boy, lunatics and possessed are there painted. The magnificent compositions of the miraculous recovery of a patient with ascites (debela, vodena bolest) and these affected by disorders of mainly neuromuscular and locomotor systems are performed by talented masters. The King Stefan Urosh Dechanski Third (1322-1331) founded the hospital in the Dechani Monastery, as a purely medical institution for providing treatment. This hospital was organized and modelled on the hospital in the Pantocrator Monastery in Constantinople. His biographer Gregory Camblak described that this hospital took in patients suffering from epilepsy (svestenoga neduga radi stradalcem) and serious nervous disorders, lepers, cripples, paralytics and those with lung diseases. Regardless of differences in the artistic level, most of these frescoes are impressively natural and realistic. This supports the ascertain that masters painted even some of patients from Monastery Hospital. The scenes of Christ's miraculous recoveries in the Dechani Monastery are undoubtelly significant for both the cultural history and the Serbian medieval medicine. This considerable cycle of the monumental painting and frescoes with medical matter, constitutes the basis for research of the Serbian medicine of the Middle-Ages.