Six new cases confirm the clinical molecular profile of complete combined 17 alpha-hydroxylase/17,20-lyase deficiency in Brazil

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17 alpha-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17 alpha-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (> 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium ( 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17 alpha-hydroxylase/17,20-lyase deficiency in Brazilian patients. Arq Bras Endocrinol Metab. 2010;54(8):711-6548SI71171

Budget impact analysis of medicines : updated systematic review and implications

This evaluation determines whether published studies to date meet the key characteristics identified for budget impact analyses (BIA) for medicines, accomplished through a systematic review and assessment against identified key characteristics. Studies from 2001 to 2015 on "budget impact analysis" with "drug" interventions were assessed, selected based on their titles/abstracts and full texts, with their characteristics checked according to key criteria. Out of 1984 studies, 92 were identified. Of these, 95% were published in Europe and the USA. 2012 saw the largest number of publications (16%) with a decline thereafter. 48% met up to 6 or 7 out of the 9 key characteristics. Only 22% stated no conflict of interest. The results indicate low adherence to the key characteristics that should be considered for BIAs and strong conflict of interest. This is an issue since BIAs can be of fundamental importance in managing the entry of new medicines including reimbursement decisions

Disorders of sex development: effect of molecular diagnostics

Disorders of sex development (DSDs) are a diverse group of conditions that can be challenging to diagnose accurately using standard phenotypic and biochemical approaches. Obtaining a specific diagnosis can be important for identifying potentially life-threatening associated disorders, as well as providing information to guide parents in deciding on the most appropriate management for their child. Within the past 5 years, advances in molecular methodologies have helped to identify several novel causes of DSDs; molecular tests to aid diagnosis and genetic counselling have now been adopted into clinical practice. Occasionally, genetic profiling of embryos prior to implantation as an adjunct to assisted reproduction, prenatal diagnosis of at-risk pregnancies and confirmatory testing of positive results found during newborn biochemical screening are performed. Of the available genetic tests, the candidate gene approach is the most popular. New high-throughput DNA analysis could enable a genetic diagnosis to be made when the aetiology is unknown or many differential diagnoses are possible. Nonetheless, concerns exist about the use of genetic tests. For instance, a diagnosis is not always possible even using new molecular approaches (which can be worrying for the parents) and incidental information obtained during the test might cause anxiety. Careful selection of the genetic test indicated for each condition remains important for good clinical practice. The purpose of this Review is to describe advances in molecular biological techniques for diagnosing DSDs

Deafness resulting from mutations in the GJB2 (connexin 26) gene in Brazilian patients

Congenital deafness occurs in approximately 1 in 1000 live births. In developed countries about 60% of hearing loss is genetic. However, in Brazil most cases of hearing loss are due to environmental factors, such as congenital infections (mainly rubella), perinatal anoxia, kernicterus and meningitis. Recently, it has been demonstrated that the GJB2 gene is a major gene underlying congenital sensorial deafness. Mutations in this gene cause 10-20% of all genetic sensory hearing loss. One specific mutation, 35deIG, accounts for the majority of mutant alleles. The extent of the hearing impairment varies from mild/moderate to profound, even within the patients homozygous for the common 35deIG mutation. There may also be progression with age. Mutation analysis in the GJB2 gene was performed on 36 families (group A) presenting with at least one individual with non-syndromic deafness (NSD). An unselected series of 26 deaf individuals referred by other services where the environmental factors were not completely excluded was also part of the study (group B). Mutations in the GJB2 gene were found in 22% (eight patients) of the families tested in group A, and 11.5% (three patients) of individuals within group B. This finding should facilitate diagnosis of congenital deafness and allow early treatment of the affected subjects.61535435

A rare case of aniridia and balanced translocation (5;11) (p15.3; q22) arising in the same subject: A challenge for genetic counseling

A rare case of aniridia and balanced translocation (5:11)(p15.3;q22) arising in the same subject: et challenge for genetic counseling: The authors report on a case of isolated aniridia caused by haploinsufficiency of the PAX6 gene, which is located on 11p13, and a balanced translocation t(5;11)(p15.3;q22) inherited respectively from his father and his mother. Due to the coincidence of two abnormalities in the same chromosome, the segregation of the mutant allele leading to aniridia and of the chromosomes involved in the translocation are not independent events. Considering that both monosomy and trisomy for 11q22-qter are unviable, his offspring may inherit either the PAX6 mutation or the balanced translocation. However, depending on the occurrence of crossing over, there is a possibility for him to have normal offspring; on the other hand, he may also father children with both anomalies. This unusual case, in which the proband has a presumably very low chance of completely normal offspring, turned to be a challenge for genetic counseling.171495

Idiopathic male pseudohermaphroditism is associated with prenatal growth retardation

About 50% of intersex cases are due to male pseudohermaphroditism, and of these cases, 50% are not clarified aetiologically. The association of idiopathic male pseudohermaphroditism and prenatal growth retardation has been recently reported. The aim of this study was to verify whether there was a difference in weight and/or length at birth between idiopathic and non-idiopathic male pseudohermaphroditism patients. A total of 70 patients with male pseudohermaphroditism were recruited; 35 non-idiopathic and 35 idiopathic. Birth weight and length were converted to z scores, and the severity of genital ambiguity was classified according to Prader grades: less virilised (Prader 1 to 3) and more virilised (Prader 4 or 5). Data were analysed using a Mann-Whitney test, odds ratio and logistic regression analysis. Birth weight ( P =0.028) and length ( P =0.01) z scores were lower in the idiopathic male pseudohermaphroditism group compared to the non-idiopathic group and were also significantly decreased among the less virilised patients, both in the sample as a whole (weight z score, P =0.002; length z score, P =0.0008) and in the group of idiopathic patients (weight z score, P =0.013; length z score, P =0.007). According to logistic regression analysis, only birth length z score significantly predicted the severity of the genital ambiguity in patients with idiopathic male pseudohermaphroditism ( P =0.0007). Conclusion:There is an association between prenatal growth retardation and male pseudohermaphroditism which may be due to genetic factors not clarified yet or to environmental factors which act early in gestation.164528729

Turner's syndrome and thyroid disease: A transverse study of pediatric patients in Brazil

An increased prevalence of autoimmune thyroid disease (AITD) has been described in Turner's syndrome (TS), but the extent of this association is still controversial. Some studies also suggest that AITD is more frequent among patients with X-isochromosome. In order to determine the prevalence of AITD among girls with TS, and to look for an association with age and karyotype, we evaluated 71 patients with a mean age of 11.4 years (range 0-19.9), 15.5% (11/71) were hypothyroid, 17 (23.9%) mere positive for thyroid peroxidase (TPO) and/or thyroglobulin (Tg) antibodies, and 24 (33.8%) had thyromegaly. No abnormality was observed before 4 years, and the highest frequencies were observed after 16 years. There were no significant differences concerning thyroid findings among patients with a 45,X karyotype, mosaics, and structural rearrangements. Half of the patients (35/71) exhibited one or more abnormalities, which demonstrates the importance of careful evaluation of thyroid function in all girls with TS.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.13435736

Complete XY gonadal dysgenesis due to p.D293N homozygous mutation in the NR5A1 gene: a case study

The SRY gene (sex-determining region on the Y chromosome; MIM *480000) is responsible for initiating male gonadal development. However, only 15-20% of the cases of XY gonadal dysgenesis are due to mutations in its sequence. Recently, heterozygous mutations in the NR5A1 gene (nuclear receptor subfamily 5, group A. member 1; MIM +184757) have been described in association with ovarian failure and disorders of testis development with or without adrenal failure. Here we describe a case of XY complete gonadal dysgenesis due to a p.D293N homozygous mutation in the NR5A1 gene, with normal SRY and no adrenal failure.51222322

Detection of Gly-196-Ser mutation in 5 alpha-reductase type II gene in a Brazilian patient with female assignment and behavior

We describe the identification of a single base mutation in the 5 alpha-reductase type II gene in a Brazilian patient who was reared as female and remained with female behavior and sexual identity.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.11346546

Social skills in women with Turner Syndrome

The aim of this study was to evaluate the performance of a group of women with Turner Syndrome (TS) in interpersonal situations where several social skills were required, and to compare the results with unaffected sisters. Fifty-two TS females aged 15-35 years and 33 sisters aged 16-43 were evaluated using Del-Prette Social Skills Inventory (SSI) and individual interviews. Thirty mothers to subjects and sisters answered questionnaires. It was found that TS girls' performance in SSI was as good as their sisters' and even better in meeting new people and facing unknown situations (p = 0.020). Older TS women scored better than younger ones, differently from their sisters. There were no significant correlations between total score of TS women and their age at diagnosis, time of follow-up and height z-score. Mothers reported having more problems with TS girls than with sisters. Although TS girls demonstrated having social difficulties, just a few of them spontaneously complained about interpersonal problems in the interview. Results suggest that social difficulties may not cause TS girls major problems nor make them unhappy with their social lives, and/or TS girls may not be able to perceive their own difficulties. Good performance in SSI also suggests that TS girls can identify adequate skills in presented situations and answer in a way to obtain good scores, but they may not necessarily use their skills due to other factors like anxiety and shyness. They may also have a tendency to answer SSI in a way they consider socially desirable, masking their real difficulties.52544044