Ataxia de Friedreich, revisión y actualización de la literatura con búsqueda sistemática de casos en Latinoamérica / Friedreich's ataxia, review and literature update with a systematic search for cases in Latin America

La Ataxia de Friedreich (AF) es una enfermedad neurodegenerativa autosómica recesiva con compromiso multisistémico. En esta revisión, se actualizan aspectos epidemiológicos, fisiopatológicos y clínico-terapéuticos y se conduce una búsqueda sistemática de casos de AF reportados en Latinoamérica. La prevalencia de AF en poblaciones caucásicas es estimada entre 2 y 5 casos por 100 000 habitantes. En Latinoamérica se han publicado 35 estudios que reúnen 1481 casos en 6 países. Causada por la expansión anormal de repeticiones GAA en el gen FXN, la etiopatogenia está asociada a una reducción en los niveles de la proteína frataxina (que altera el metabolismo energético) y el acúmulo de hierro mitocondrial. El fenotipo clásico de AF suele comenzar antes de los 25 años, aunque hay otros de inicio tardío y retención de reflejos. La sintomatología se caracteriza por ataxia progresiva, alteración sensitiva, arreflexia, disartria, y alteraciones oculomotoras, además de compromiso cardiaco, endocrino y musculoesquelético. El diagnóstico requiere evaluación neurológica detallada, estudios neurofisiológicos, neuroimágenes y pruebas bioquímicas pero el enfoque determinante es el estudio genético que demuestre variantes genéticas bialélicas en el gen FXN. El manejo es multidisciplinario, orientado a aminorar los síntomas, prevenir complicaciones y brindar asesoramiento genético apropiado. Recientemente se ha aprobado el primer tratamiento farmacológico para AF con varios más en fases de experimentación.

SUMMARY Friedreich Ataxia (FA) is an autosomal recessive neurodegenerative disease with multisystemic involvement. This update of epidemiological, pathophysiological, and clinico-therapeutic aspects of FA, includes a systematic review of cases in Latin America. The estimated FA prevalence in Caucasian populations is between 2 to 5 cases per 100 000. In Latin America, 1481 cases have been published in 35 articles from six different countries. Caused by an abnormally repeated expansion of GAA trinucleotide inside the FXN gene, FA's etiopathogenesis is associated with reduced levels of the frataxin protein, which disturb the energy metabolism and result in mitochondrial iron accumulation. The classic phenotype usually shows symptoms before the age of 25, although there are others with a later onset. The main symptoms of AF are progressive ataxia, sensory disturbances, areflexia, dysarthria, and oculomotor alterations, in addition to cardiac, endocrine, and musculoskeletal compromise. Diagnostic workup requires a detailed neurological examination, neuroconduction studies, neuroimaging, and biochemical tests. The definitive diagnosis is provided by genetic testing showing biallelic variants within the FXN gene. The management is multidisciplinary, aimed at reducing symptoms, preventing complications, and providing an appropriate genetic counseling. Recently, the first pharmacological treatment for AF has been approved, with several others in clinical assessment trials.

Recent recommendations from ATA guidelines to define the upper reference range for serum TSH in the first trimester match reference ranges for pregnant women in Rio de Janeiro

ABSTRACT Objectives: American Thyroid Association (ATA)'s new guidelines recommend use of population-based trimester-specific reference range (RR) for thyrotropin (TSH) in pregnancy. The aim of this study was to determine first trimester TSH RR for a population of pregnant women in Rio de Janeiro State. Subjects and methods: Two hundred and seventy pregnant women without thyroid illness, defined by National Academy of Clinical Biochemistry, and normal iodine status were included in this sectional study. This reference group (RG) had normal median urinary iodine concentration (UIC = 219 μg/L) and negative anti-thyroperoxidase antibodies (TPOAb). Twin pregnancy, trophoblastic disease and use of drugs or supplements that influence thyroid function were excluded. In a second step, we defined a more selective reference group (SRG, n = 170) by excluding patients with thyroiditis pattern on thyroid ultrasound and positive anti-thyroglobulin antibodies. This group also had normal median UIC. At a final step, a more selective reference group (MSRG, n = 130) was defined by excluding any pregnant women with UIC < 150 μg/L. Results: In the RG, median, 2.5th and 97.5th percentiles of TSH were 1.3, 0.1, and 4.4 mIU/L, respectively. The mean age was 270 ± 5.0 and the mean body mass index was 25.6 ± 5.2 kg/m2. In the SRG and MSRG, 2.5th and 975th percentiles were 0.06 and 4.0 (SRG) and 0.1 and 3.6 mIU/L (MSRG), respectively. Conclusions: In the population studied,TSH upper limit in the first trimester of pregnancy was above 2.5 mIU/L. The value of 3.6 mIU/L, found when iodine deficiency and thyroiditis (defined by antibodies and ultrasound characteristics) were excluded, matches recent ATA guidelines.

Changes of thyroid function, thyroid antibodies and urinary iodine among permanent residents of Urumqi in Xinjiang / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the rates of diagnosis on thyroid disease and the differences in the distribution of age groups among those permanent residents, to analyze the relationships among thyroid function, thyroid antibodies and urinary iodine.</p><p><b>METHODS</b>A cross-sectional survey was performed in 1 995 permanent residents in Urumqi, Xinjiang in May, 2013, Among them, 1 906 were healthy adults aged 18-84 age, with mean age as (46.3 ± 14.2) years and 30.4% of them were men. One time 10 ml random urine and blood samples were drown to examine urinary iodine (UI) thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroglobulin (TgAb) and anti-thyroid peroxidase (TPOAb).</p><p><b>RESULTS</b>1) 213 residents were newly diagnosed as having thyroid dysfunction (11.2%, including 78.4% women), hyperthyroidism (clinical and subclinical hyperthyroidism) that accounted for 2.7%, hypothyroidism (clinical and subclinical hypothyroidism) was accounted for 8.5%. Positive rates of TgAb (23.2%), TPOAb (16.6%) were noticed. The median urinary iodine was 134.5 µg/L, with 32% of the subjects were having iodine deficiency, 58% having adequate iodine and another 10% as under excessive iodine. No differences were observed on urine iodine between thyroid dysfunction and euthyroidism or between subjects with positive and negative antibodies. 2) TSH appeared different among age-groups of 18-, 45- and over 60. TSH showed higher in women than in men, with P value as < 0.001. For people with euthyroidism, TSH level in the antibody positive group was significantly higher than the antibody negative group (P < 0.000 1). 3) For people over 60 of age, morbidity of hypothyroidism was significantly higher than those under 60 but with no differences related to hyperthyroidism or the antibody positive rate.</p><p><b>CONCLUSION</b>UI levels were not significantly related with thyroid function and thyroid antibodies among residents of Urumqi, women showed higher on thyroid dysfunction or the rate of positive antibody. In the antibody positive group, TSH levels were significantly higher than in the antibody negative group. Hypothyroidism was seen higher in the over 60-years-of-age population. Monitoring programs on thyroid function, thyroid antibodies and urinary iodine among people over 60-years-of-age, should be strengthened.</p>

Association of thyroperoxidase gene polymorphisms with dyshormonogenesis in congenital hypothyroidism / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of thyroperoxidase (TPO) gene polymorphisms with dyshormonogenesis in congenital hypothyroidism (CH).</p><p><b>METHODS</b>The 17 exons and flanking introns of the TPO gene from 30 randomly selected samples were sequenced for the selection of single nucleotide polymorphisms (SNPs). In 136 patients with dyshormonogenetic CH and 141 healthy controls from the same region, the selected SNPs were genotyped by polymerase chain reaction (PCR) and direct sequencing or PCR-restriction fragment length polymorphism (RFLP).</p><p><b>RESULTS</b>Six SNPs (rs9678281, rs376413622, rs1126797, rs4927611, rs732609 and rs1126799) were selected to determine the genotype for each sample. Among these, rs4927611 and rs732609 showed a significant difference between the two groups in both allelic and genotypic frequencies. With a recessive model of inheritance, rs732609 CC (OR=0.484, 95%CI: 0.253-0.927, P=0.04) and rs4927611 TT (OR=0.32, 95%CI: 0.112-0.915, P=0.047) were greater in the patients.</p><p><b>CONCLUSION</b>rs4927611 and rs732609 may be associated with dyshormonogenetic CH. rs4927611 TT and rs732609 CC are genotypes associated with potential risk for the disease.</p>

Sobre escravos e genes: “origens” e “processos” nos estudos da genética sobre a população brasileira / On slaves and genes: “origins” and “processes” in genetic studies of the Brazilian population

Neste artigo examino como geneticistas contemporâneos que pesquisam a história e a configuração da população brasileira interagem com outras disciplinas. Para tanto, tomei como estudo de caso artigos publicados por geneticistas que investigam a presença de variantes da hemoglobina S no Brasil, os quais pretendem claramente contribuir para a análise de questões como escravidão ou identidade étnica no país. Contrastando esses estudos com trabalhos contemporâneos da história e das ciências sociais, problematizo a centralidade explanatória da “origem” nos estudos genéticos analisados, bem como a falta de interação com questões epistemológicas de outras áreas do saber.

In this article I examine how contemporary geneticists investigating the history and configuration of the Brazilian population engage with other academic disciplines. To do so I use as a case study some articles published by geneticists researching the presence of hemoglobin S variants in Brazil, in which there is a clear pretension to contribute to the analysis of issues such as slavery or Brazil’s ethnic identity. By contrasting these studies with contemporary works from history and the social science, the explanatory centrality of “origin” in the genetic studies analyzed is problematized, as is the lack of interaction with the epistemological characteristics of other areas of knowledge.

Molecular and clinical investigation of Iranian patients with Friedreich ataxia

Friedreich ataxia [FRDA] is an autosomal recessive disorder caused by guanine-adenine-adenine [GAA] triplet expansions in the FXN gene. Its product, frataxin, which severely reduces in FRDA patients, leads to oxidative damage in mitochondria. The purpose of this study was to evaluate the triple nucleotide repeated expansions in Iranian FRDA patients and to elucidate distinguishable FRDA clinical differences in these patients. A number of 22 Iranian patients [8 females and 14 males] from 16 unrelated families were studied. DNA was extracted from the peripheral blood of patients. The frequency and length of [GAA]n repeats in intron 1 of the FXN gene were analyzed using long-range PCR. In this study, the clinical criteria of FRDA in our patients and the variability in their clinical signs were also demonstrated. An inverse relationship was observed between GAA repeat size and the age of onset. Although some distinguishable clinical features [such as limb ataxia and lower limb areflexia] were found in our patients, 90-95% of them had extensor plantar response and dysarthria. The results showed only one positive diabetes patient and also different effects on eye movement abnormality among our patients. The onset age of symptoms showed a significant inverse correlation with allele size in our patients [P>0.05]. Based on comparisons of the clinical data of all patients, clinical presentation of FRDA in Iranian patients did not differ significantly from other FRDA patients previously reported

Thyroid ultrasound findings associated with thyroid peroxidase autoantibody positivity in patients with diffuse goiter

BACKGROUND: To determine the thyroid ultrasound findings in association with anti-TPO positivity among patients with diffuse goiter.DESIGN AND METHODS: We performed a cross-sectional study on patients with diffuse goiter seen at Makati Medical Center out-patient Endocrine clinics from October 1, 2011 to October 1, 2012. Patients with anti-TPO (thyroid peroxidase) above 100 pmol/L were considered anti-TPO positive and below this level were considered negative. After excluding patients with other possible causes of thyroiditis, thyroid ultrasound of anti-TPO positive and anti-TPO negative patients were reviewed and compared based on size, echogenicity, echopattern and vascularity of the thyroid parenchyma.RESULTS: In 94 patients who qualified for the study, 43.6% were anti-TPO positive. A higher proportion of anti-TPO positive was seen among females compared to males by almost twofold (49.7% vs 25%, p0.05). Stratified according to age group for female patients, anti-TPO positivity is relatively higher among 31-50 years old (51.1%, p =0.753). Among male, anti-TPO positivity is present in all 18-2 years old which is significantly higher compared to other age group (p larger thyroid size in all measurement parameters (p= 0.0053). Among anti-TPO positive patients, frequent ultrasound findings were: hypoechoic (79% vs. 21%, p 0.001); heterogenous parenchyma (71% vs. 29%, p 0.001) and increased vascularity (93% vs. 7%, p 0.001). Of note is the absence of homogenous prenchyma fnding among anti-TPO positive. All 23 (100%) patients who showed combined findings of hypoechoic, heterogenous parenchyma and increased vascularity were anti-TPO positive.CONCLUSION: Thyroid ultrasound findings that are found frequently among anti-TPO positive are increased thyroid size, parenchyma that are hypoechoiec and heterogenous and increased vascularity. Homogenous echotexture was not seen among anti-TPO positive. The combined sonographic characteristics of hypoechoic, heterogenous pattern and increased vascularity are highly suggestive of presence of anti-TPO (100%).

Avances en el tratamiento de las ataxias crónicas / [Therapeutic developments in chronic ataxias].

Autosomal recessive cerebellar ataxias belong to a broader group of disorders known as inherited ataxias. In most cases onset occurs before the age of 20. These neurological disorders are characterized by degeneration or abnormal development of the cerebellum and spinal cord. Currently, specific treatment is only available for some of the chronic ataxias, more specifically those related to a known metabolic defect, such as abetalipoproteinemia, ataxia with vitamin E deficiency, and cerebrotendinous xanthomatosis. Treatment based on a diet with reduced intake of fat, supplementation of oral vitamins E and A, and the administration of chenodeoxycholic acid could modify the course of the disease. Although for most of autosomal recessive ataxias there is no definitive treatment, iron chelators and antioxidants have been proposed to reduce the mitochondrial iron overload in Friederich’s ataxia patients. Corticosteroids have been used to reduce ataxia symptoms in ataxia telangiectasia. Coenzyme Q10 deficiency associated with ataxia may be responsive to Co Q10 or ubidecarenone supplementations. Early treatment of these disorders may be associated with a better drug response.

Production and application of polyclonal antibody against mouse frataxin / 生物工程学报

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by reduced expression levels of the frataxin gene (FXN) due to expansion of triplet nucleotide GAA repeats in the first intron of FXN. FXN is a mitochondrial protein which plays an important role in the regulation of intracellular iron trafficking, biogenesis of iron-sulfur cluster and heme, and removal of reactive oxygen species. Our previous work showed that tissue-specific expression of FXN in cerebellum and heart generates two novel isoforms. In order to find the isoforms in mouse tissues, we tried to obtain a polyclonal antibody against mouse Fxn with high specificity and sensitivity. Thus, the recombinant plasmid pET24(+)-mFxn was constructed to express his-tagged Fxn in BL21 (DE3) cells. The expressed protein is a mature form with 130 amino acids (aa, 14.38 kDa) without the N-terminal signal peptide (77 aa), purified on Ni-NTA column and further dialyzed with Centrifugal Filtration Device. The polyclonal antibody against Fxn was produced by immunizing rabbits with highly purified protein. The collected antiserums were preliminarily purified by precipitation with (NH4)2SO4. Western blotting analysis and cell immunofluorescence showed that the obtained antibody was able to detect both purified and endogenous Fxn. It also worked well in immunoprecipitation with mouse tissues. This is the first time, to our knowledge, to report that mouse Fxn was used as immunogen to generate antibody with high specificity and sensitivity. This work provides a powerful tool for our further research on mouse Fxn isoforms.

Relationship of iron overload to bone mass density and bone turnover in postmenopausal women with fragility fractures of the hip / 中华外科杂志

<p><b>OBJECTIVE</b>To study relationships between serum ferritin and bone metabolism in patients with hip fragility fractures.</p><p><b>METHODS</b>This cross-sectional study included 76 postmenopausal women with hip fracture from Feburary 2011 to June 2012. The mean age of the women was (73 ± 10) years (range, 55-93 years) and the mean duration of menstruation was (22 ± 10)years (range, 5-50 years). Serum concentrations of ferritin, transferrin, alkaline phosphatase (ALP), amino-terminal extension peptide of type I collagen (P1NP), C-terminal telopeptides of type I collagen (β-CTX)and femoral and lumbar bone mineral density by dual-energy X-ray absorptiometry were measured. Bone metabolism was compared between normal and elevated ferritin groups with t-test, Pearson linear, partial correlation and multiple regression analysis examined associations between iron- and bone-related markers.</p><p><b>RESULTS</b>Serum ferritin concentration raised to (230 ± 146)µg/L, transferrin concentration reduced to (1.89 ± 0.33)g/L. P1NP concentration raised to (61 ± 32) ng/L when the concentration of serum ALP and β-CTX were in the normal range. T-scores for bone mineral density in the femoral neck (-2.0 ± 1.1) and lumbar (-2.1 ± 1.2) were below the normal ranges(-1.0-1.0). The subjects were divided into two groups according to serum ferritin concentration, normal group(serum ferritin concentration ≤ 150 µg/L, n = 25) and elevated group(serum ferritin concentration > 150 µg/L, n = 51). Patients of elevated group had lower bone mineral density in femoral neck and lumbar than normal group(t = 3.13,2.89, P < 0.01), and higher P1NP, β-CTX concentration (t = -2.38, -3.59, P < 0.05) . In partial correlation analysis adjusted for confounders, serum ferritin concentration was correlated negatively with bone mineral density in both femoral neck and lumbar (r = -0.335,-0.295, P < 0.05), and positively with P1NP and β-CTX (r = 0.467,0.414, P < 0.05), but not correlated with ALP (r = 0.188, P > 0.05). Transferrin concentration tended to be correlated positively with bone mineral density in both femoral neck and lumbar (r = 0.444, 0.262, P < 0.05) and negatively with ALP, P1NP and β-CTX(r = -0.326,-0.285,-0.278, P < 0.05).</p><p><b>CONCLUSIONS</b>Iron overload has a high prevalence in postmenopausal women with fragility fracture. Increased iron stores, which might lead to bone loss and lower bone mineral density by enhancing the activity of bone turnover, could be an independent factor to take effects on bone metabolism on postmenopausal women.</p>

Identification of RNA-binding sites in artemin based on docking energy landscapes and molecular dynamics simulation

There are questions concerning the functions of artemin, an abundant stress protein found in Artemia during embryo development. It has been reported that artemin binds RNA at high temperatures in vitro, suggesting an RNA protective role. In this study, we investigated the possibility of the presence of RNA-binding sites and their structural properties in artemin, using docking energy landscapes and molecular dynamics simulation. Analysis of docking energy landscapes revealed sites in artemin with the potential of binding RNAs. We found a good agreement between RNA-binding sites of artemin and RNA-interacting sites of a specific group of RNA-binding proteins called PUF, as regards to the type of their interactions with RNA molecules. Furthermore, the results from molecular dynamics simulation showed that firstly, the presence of RNA molecule and its interaction with artemin cause significant decrease in the secondary structure content of artemin; secondly, RNA-binding sites are mostly located in the low flexible regions. Finally, it seems that these binding sites are distributed in such a way that leads RNA molecule into the interior of the protein, strengthening the previous suggestion for RNA-pro-tecting role of artemin

Study of FRDA gene in suspect Friedreich ataxia patients

Friedreich ataxia [FA] is an autosomal recessive disorder. Cause of about 2-4% of disease is a GAA triplet repeat expansion in the one allele and carries a point mutation as the other allele. This study was performed to investigate exons of FXN gene to find point mutations for the first time in Iran. In this descriptive study, 50 patients suspected to FA who referred to Special Medical Center were investigated. Genomic DNA was investigated by different PCR methods, including PCR for intron, Long PCR and PCR for exons of FXN gene. Then, products were sequenced and finally sequences were analyzed by related software. C to G nucleotide in intron 2 nt:825954, and T to C in intron 3 nt:832729 of FRDA gene were observed by sequencing method. Nucleotide G insertion was detected in exon 5a nt: 822225. Our study showed that diagnosis of FA is not simple because of clinical overlapping with other ataxia, some mutations in intron maybe affect on the disease which need more examination, and because of consanguinity marriage in Iran, some patients with homozygote mutation may show FA phenotype

Prevalence of thyroid dysfunction among asymptomatic elderly Filipinos at the Philippine General Hospital / Journal of the ASEAN Federation of Endocrine Societies

The elderly are a peculiar group in terms of health management, as they often present with non-specific complaints which are challenging to interpret and may not present with the usual clinical picture of a disease. Objective. The study aims to determine the prevalence of thyroid dysfunction among asymptomatic, elderly Filipinos seen at the Philippine General Hospital (PGH). Methodology. Subjects aged 60 years and older seeking out-patient medical consult for non-thyroidal illness at the PGH were recruited. Patients with known thyroid or pituitary disease, previous thyroid or pituitary surgery, intake of medications known to affect thyroid hormone levels and critical illness were excluded. Fasting blood sugar (FBS), lipid profile, free thyroxine (FT4), thyroid-stimulating hormone (TSH), and anti-thyroperoxidase (anti-TPO) levels were taken. Based on FT4 and TSH levels, subjects were classified as overt hypothyroid, subclinical hypothyroid, euthyroid, subclinical hyperthyroid, or overt hyperthyroid. Results. One hundred eighty subjects were recruited, of whom 152 (84%) were female. Hypertension was the most common comorbidity (58.33%), followed by diabetes (36.67%). One hundred sixty-two (90%) were euthyroid, 12 (6.7%) subclinical hypothyroid, 4 (2.22%) subclinical hyperthyroid, and two (1.11%) overtly hyperthyroid. No one was overtly hypothyroid. There was a trend toward increasing prevalence of diabetes, hypertension, low HDL, obesity and overall cardiovascular risk among those with subclinical hypothyroidism. Conclusion. Subclinical hypothyroidism was the most prevalent thyroid dysfunction among asymptomatic elderly included in the study.

[Association of T2229/C exon 12 polymorphisms of thyroid peroxidase gene with anti-TPO levels in Tehran population]

Antibody secretion in human may be the result of the changes in protein structure. Probably these changes in protein structure or polymorphism in human thyroid peroxidase [TPO] gene is the reason for presence of the anti TPO. In this study, we examined the association of T2229/C exon 12 polymorphism of TPO gene in respect to anti-TPO level. In this study 168 individuals [47 +/- 2 years] were selected as case and control groups based on anti-TPO titer above and below 100 IU/L. PCR-RFLP [polymerase chain reaction-restriction fragment length polymorphism] was used to amplify the segment of exon 12 polymorphism. In exon 12 the allele frequencies were 0.8698 for C allele and 0.1301 for T allele and there was no significant association between this polymorphism and anti-TPO level [CC=127.5 +/- 308 IU/ml vs. TT=126 +/- 224 IU/ml]. This study indicated that there is no significant association between anti-TPO levels and T2229/C exon 12 polymorphisms. Meanwhile, selected SNP of exon12 directly has no effect on anti-TPO levels

Telomerase reverse transcriptase promoter-driven expression of iodine pump genes for targeted radioiodine therapy of malignant glioma cells / 癌症

Radioiodine is a routine therapy for differentiated thyroid cancers. Non-thyroid cancers can intake radioiodine after transfection of the human sodium iodide symporter (hNIS) gene. The human telomerase reverse transcriptase (hTERT) promoter, an excellent tumor-specific promoter, has potential value for targeted gene therapy of glioma. We used the hTERT promoter to drive the expression of the hNIS and human thyroid peroxidase (hTPO) gene as a primary step for testing the effects of radioiodine therapy on malignant glioma. The U87 and U251 cells were co-transfected with two adenoviral vectors, in which the hNIS gene had been coupled to the hTERT promoter and the hTPO gene had been coupled to the CMV promoter, respectively. Then, we performed Western blot, 125I intake and efflux assays, and clonogenic assay with cancer cells. We also did 99mTc tumor imaging of nude mice models. After co-transfection with Ad-hTERT-hNIS and Ad-CMV-hTPO, glioma cells showed the 125I intake almost 1.5 times higher than cells transfected with Ad-hTERT-hNIS alone. Western blots revealed bands of approximately 70 kDa and 110 kDa, consistent with the hNIS and hTPO proteins. In clonogenic assay, approximately 90% of co-transfected cells were killed, compared to 50% of control cells after incubated with 37 MBq of 131I. These results demonstrated that radioiodine therapy was effective in treating malignant glioma cell lines following induction of tumor-specific iodide intake by the hTERT promoter-directed hNIS expression in vitro. Co-transfected hNIS and hTPO genes can result in increased intake and longer retention of radioiodine. Nude mice harboring xenografts transfected with Ad-hTERT-NIS can take 99mTc scans.

Mutation of thyroid peroxidase gene in 35 patients with congenital hypothyroidism / 中华儿科杂志

<p><b>OBJECTIVE</b>To identify thyroid peroxidase (TPO) gene mutations in 35 patients with congenital hypothyroidism.</p><p><b>METHOD</b>Genomic DNA was isolated from peripheral blood samples of 35 patients with congenital hypothyroidism. All of the 17 exons and flanking introns of TPO gene were amplified by PCR, then the PCR products were sequenced bi-directionally and were analyzed by restriction endonucleases.</p><p><b>RESULT</b>One patient had compound heterozygous mutations c.961A>G/c.2422delT, one was c.2268insT/c.1477G>A, and three was homozygous mutation c.2268insT. The TPO gene mutation c.961A>G [p. Thr321Ala] was one novel mutation.</p><p><b>CONCLUSION</b>High frequency mutation in TPO gene was detected in patients with congenital hypothyroidism.</p>

Monoallelic thyroid peroxidase gene mutation in a patient with congenital hypothyroidism with total iodide organification defect / Mutação monoalélica no gene da tireoperoxidase em paciente com hipotireoidismo congênito com defeito total de incorporação de iodeto

The aim of this study was to identify the genetic defect of a patient with dyshormonogenetic congenital hypothyroidisms (CH) with total iodide organification defect (TIOD). A male child diagnosed with CH during neonatal screening. Laboratory tests confirmed the permanent and severe CH with TIOD (99 percent perchlorate release). The coding sequence of TPO, DUOX2, and DUOXA2 genes and 2957 base pairs (bp) of the TPO promoter were sequenced. Molecular analysis of patient's DNA identified the heterozygous duplication GGCC (c.1186_1187insGGCC) in exon 8 of the TPO gene. No additional mutation was detected either in the TPO gene, TPO promoter, DUOX2 or DUOXA2 genes. We have described a patient with a clear TIOD causing severe goitrous CH due to a monoallelic TPO mutation. A plausible explanation for the association between an autosomal recessive disorder with a single TPO-mutated allele is the presence of monoallelic TPO expression.

O objetivo deste estudo foi identificar defeitos genéticos em paciente com hipotireoidismo congênito (HC) por disormonogênese e defeito total de incorporação de iodeto (DIIT). Neonato do sexo masculino com HC diagnosticado pelo rastreamento neonatal. Exames clínicos e radiológicos confirmaram que o paciente apresentava HC severo e permanente com DIIT (teste de perclorato: 99 por cento). A região codificadora dos genes TPO, DUOX2, DUOXA2 e 2957 pares de bases (pb) do promotor de TPO foram sequenciados. No paciente foi identificada a duplicação em heterozigose GGCC no éxon 8 do gene TPO (c.1186_1187insGGCC). Nenhuma outra mutação foi localizada nos genes TPO, incluindo o promotor, DUOX2 ou DUOXA2. Descrevemos paciente com grave defeito de organificação de iodeto, provocando HC severo com bócio, em consequência de uma única mutação monoalélica no gene TPO. A expressão monoalélica no tecido tireoideano explicaria a associação de uma doen­ça autossômica recessiva com uma única mutação monoalélica.

Serum levels of ferritin, iron and total iron binding capacity in patients with recurrent aphthous stomatitis

Recurrent aphthous stomatitis is the most common oral disease yet despite its high prevalence, the etiological factor [s] of this ulcer is not fully understood. The aim of this study was to determine the serum levels of ferritin, iron, and TIBC in patients with RAS. This case-control study was performed on 40 patients with RAS and 40 healthy people [control group]. They were screened through laboratory tests for the indices mentioned above. The data was analyzed by SPSS, chi-square and t-tests. Of 40 patients, 25.6% were found with ferritin deficiency compared to 7.5% of control group [p<0.05] however, no significant difference for other indices were observed. Low ferritin level in patients with RAS is suggesting a relation between RAS and ferritin deficiency

Expressions of RASSF1A, Galectin-3 and TPO mRNA in papillary thyroid carcinoma and their clinical significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the mRNA expressions of RASSF1A, Galectin-3 and TPO in papillary thyroid carcinoma and some other thyroid benign lesions, and evaluate their diagnostic significance.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of RASSF1A, galectin-3 and TPO in the samples from 73 cases, including 23 cases with papillary thyroid cancer, 16 with nodular goiter, 29 with thyroid adenoma and 5 with Hashimoto's disease.</p><p><b>RESULTS</b>A statistically significant difference in the mRNA expression of RASSF1A, Galectin-3 and TPO was observed between papillary thyroid carcinoma and follicular benign lesions (P<0.05). However, there was no significant difference among various kinds of benign lesions (P>0.05). A negative correlation of the expression of RASSF1A and Galectin-3 mRNA was found between thyroid benign lesions and malignant ones (P = 0.000). While the mRNA expression of RASSF1A and TPO was positively correlated between benign and malignant lesions (P = 0.028).</p><p><b>CONCLUSION</b>Loss of expression of RASSF1A and TPO mRNA but high expression of Galectin-3 mRNA in papillary thyroid carcinoma are common. Therefore, the products of these three genes may be closely related to the development of thyroid papillary carcinoma, and may be used as useful markers in differential diagnosis of papillary thyroid carcinoma from the benign lesions. The results are more reliable if this detection method is used in combination with other techniques.</p>

[Prevalence of anemia and microcytic anemia among women in north-western Tabriz]

Anemia is one of the most common disorders affecting all age groups. This cross-sectional study aimed to determine the prevalence of anemia and microcytic anemia in the population served by Asadabadi Health Center in Tabriz. We used a systematic sampling method to select 1623 subjects out of a total of 233000 persons aged above 12 years. Measurements of hemoglobin, MCV [Mean Cell Volume] and in the case of anemia, serum iron, ferritin, TIBC [Total Iron Binding Capacity], together with hemoglobin electrophoresis and reticulocyte count were performed in reference laboratories. Data were analyzed using T tests and the Epi6 software package. The prevalence rate of anemia was 9.7%; more than 75% of the cases were due to iron deficiency, while 11.4% were caused by minor thalassemia. Prevalence rates for iron deficiency anemia and minor thalassemia in studied population were 7.3% and 1.1% respectively. Findings show that the degree of anemia - as defined in the WHO classification- is mild in this region. The most common cause of anemia is iron deficiency