Special issue on molecular genetics in endocrinology

Edição especial em genética molecular em endocrinologia

EDITORIAL

Special issue on molecular genetics in endocrinology

Edição especial em genética molecular em endocrinologia

Monalisa F. Azevedo^I; Regina S. Moisés^II; Sonir R. R. Antonini^III

^IServiço de Endocrinologia, Faculdade de Medicina, Hospital Universitário de Brasília, Universidade de Brasília (HUB/UnB), Brasília, DF, Brazil

^IIDisciplina de Endocrinologia, Escola Paulista de Medicina, Universidade Federal de São Paulo (Unifesp-EPM), São Paulo, SP, Brazil

^IIIEndocrinologia da Criança e do Adolescente, Departamento de Puericultura e Pediatria, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil

^{Correspondence}

Welcome to the 2012 edition of the ABEM "Clinical & Molecular Endocrine Case Reports". This special issue aims at describing clinical cases in which molecular research was performed, thus opening opportunities for the publication of novel mutations, and for the presentation of clinical particularities in patients with mutations that have already been described. Previous editions of 2008 and 2010 were highly accessed, and had great repercussion. We hope the current edition also fulfills everybody's expectations, or maybe surpasses them.

The advances in molecular genetics methods, in the recent decades, have allowed the identification of genetic components in several endocrinopathies. Many of these discoveries led to important improvements in the diagnosis and treatment of these conditions. One such example is MODY. Alterations in ten different genes have been associated with this disease, and marked differences in the clinical presentation of diabetes caused by mutations in each of these genes were noted. Patients with mutations in GCK have mild hyperglycemia, and pharmacological treatment is rarely necessary. In contrast, in individuals harboring mutations in HNF1A, hyperglycemia is progressive, and usually requires pharmacological treatment (1,2). This issue presents two studies, by DellaManna and cols. (3) and Caetano and cols. (4), in Brazilian patients with MODY 2 and harboring GCK mutations. Also in relation to the development of hyperglycemia in a monogenic context, a case of maternally-inherited diabetes and deafness (MIDD) with hyporeninemic hypoaldosteronism by Mory and cols. (5) is found in this edition.

In contrast, type 2 diabetes is notably a multifactorial and polygenic disease. The association between polymorphisms in the TCF7L2 gene and type 2 diabetes have been described in different populations in the recent years, showing a possible role of this gene in the predisposition to the disease. In this edition, such association was investigated in a Brazilian population by Barra and cols. (6).

A number of genetic alterations have been correlated with disorders in growth and sexual development, and in some cases, the genetic profile may predict the phenotype and clinical outcome. From chromosome anomalies to point mutations, studies by Maciel-Guerra and cols. (7), Keselman and cols. (8), Castro and cols. (9), Beneduzzi and cols. (10), Guaragna-Filho and cols. (11), Nishi and cols. (12), and Battistin and cols. (13) concisely address different settings of growth and/or sexual development in which molecular genetics were important tools for a proper clinical approach. Thyroid diseases were also addressed in this issue by Scaglia and cols. (14) in a case of congenital hyperthyroidism, and by Secchi and cols. (15) in a patient with transient congenital hypothyroidism. The study by Geraldo and cols. (16) illustrates the contribution of microRNA detection strategies in the prediction of outcomes, by describing a patient with an aggressive papillary thyroid carcinoma.

In pituitary diseases, better knowledge of the mechanisms involved in tumorigenesis may provide more effective medical therapy. The association of mutations in the AIP gene in patients with familial pituitary adenomas has pointed out a possible role of AIP protein alterations in the development of sporadic pituitary tumors. In this issue, Kasuki and cols. (17) investigated the AIP expression in GH-secreting tumors in correlation with response to medical treatment. Boguszewski and cols. (18) describe an interesting case in which the two types of multiple endocrine neoplasm coexist, and discuss the genetic findings associated with this condition, whereas multiple endocrine neoplasia type 2 is revisited by Blom and cols. (19) in a description of the rare S891A RET mutation in a patient with medullary thyroid carcinoma. In addition, genetic studies in oncogenic osteomalacia by Chang and cols. (20), and in Frasier (Guaragna and cols. [21]), Cowden's (Lima and cols. [22]) and hyperinsulinism/hyperammonemia (Corrêa-Giannella and cols. [23]) syndromes are presented in this issue.

In the past, knowledge about molecular genetics was important in the management of only a restricted group of patients. Currently, this strategy has become critical for proper monitoring of a large number of patients in different settings (24). Accordingly, the practitioner should be familiar with the indications and potential limitations of genetic testing.

We are honored to participate as invited editors in this Special Edition of ABEM, having the opportunity of getting in contact with high-quality articles. We would like to thank the authors who contributed to this edition submitting their manuscripts; the reviewers for their constructive comments and suggestions; and the co-editor of ABEM, Alexander A. L. Jorge, for his invaluable assistance. We hope this edition represents an opportunity to update and acquire new information in such an exciting area of ​​knowledge.

Received on Nov/16/2012

Accepted on Nov/16/2012

• 1. Fajans SS, Bell GI. MODY: history, genetics, pathophysiology and clinical decision making. Diabetes Care. 2011;34:1878-84.
• 2. Hattersley AT. Molecular genetics goes to the clinic. Clin Med. 2005;5:476-81.
• 3. DellaManna T, da Silva MR, Chacra AR, Kunii IS, Rolim AL, Furuzawa G, et al. Clinical follow-up of two Brazilian subjects with glucokinase-MODY (MODY2) with description of a novel mutation. Arq Bras Endocrinol Metab. 2012;56(8):490-5.
• 4. Caetano LA, Jorge AAL, Malaquias AC, Trarbach EB, Queiroz MS, Nery M, et al. Incidental mild hyperglycemia in children: two MODY 2 families identified in Brazilian subjects. Arq Bras Endocrinol Metab. 2012;56(8):519-24.
• 5. Mory PB, dos Santos MC, Kater CE, Moisés RS. Maternally-inherited diabetes with deafness (MIDD) and hyporeninemic hypoaldosteronism. Arq Bras Endocrinol Metab. 2012;56(8):574-7.
• 6. Barra GB, Dutra LAS, Watanabe SC, Costa PGG, da Cruz PSM, Azevedo MF, et al. Association of the rs7903146 single nucleotide polymorphism at the Transcription Factor 7-like 2 (TCF7L2) locus with type 2 diabetes in Brazilian subjects. Arq Bras Endocrinol Metab. 2012;56(8):479-84.
• 7. Maciel-Guerra AT, De Paulo J, Santos AP, Guaragna-Filho G, Andrade JGR, Siviero-Miachon AA, et al. The use of fluorescence in situ hybridization in the diagnosis of hidden mosaicism: apropos of three cases of sex chromosome anomalies. Arq Bras Endocrinol Metab. 2012;56(8):545-51.
• 8. Keselman A, Scaglia PA, Prieto MSR, Ballerini MG, Rodríguez ME, Ropelato MG, et al. Type IA isolated growth hormone deficiency (IGHD) consistent with compound heterozygous deletions of 6.7 and 7.6 Kb at the GH1 gene locus. Arq Bras Endocrinol Metab. 2012;56(8):558-63.
• 9. Castro CCTS, Guaragna-Filho G, Calais FL, Coeli FB, Leal IRL, Cavalcante-Junior EF, et al. Clinical and molecular spectrum of patients with 17-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency. Arq Bras Endocrinol Metab. 2012;56(8):533-9.
• 10. Beneduzzi D, Trarbach EB, Latronico AC, de Mendonca BB, Silveira LFG. Novel mutation in the gonadotropin-releasing hormone receptor (GNRHR) gene in a patient with normosmic isolated hypogonadotropic hypogonadism. Arq Bras Endocrinol Metab. 2012;56(8):540-4.
• 11. Guaragna-Filho G, Castro CCTS, De Carvalho RR, Coeli FB, Ferraz LFC, Petroli RJ, et al. 46,XX DSD and Antley-Bixler syndrome due to novel mutations in the cytochrome P450 oxidoreductase gene. Arq Bras Endocrinol Metab. 2012;56(8):578-85.
• 12. Nishi MY, Domenice S, Maciel-Guerra AT, Zaba Neto A, da Silva MACP, Costa EMF, et al. Analysis of anti-Müllerian hormone (AMH ) and its receptor (AMHR2 ) genes in patients with persistent Müllerian duct syndrome. Arq Bras Endocrinol Metab. 2012;56(8):473-8.
• 13. Battistin C, de Menezes Filho HC, Domenice S, Nishi MY, Manna TD, Kuperman H, et al. A novel DAX1/NR0B1 mutation in a patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism. Arq Bras Endocrinol Metab. 2012;56(8):496-500.
• 14. Scaglia PA, Chiesa A, Bastida G, Pacin M, Domené HM, Gruñeiro-Papendieck L. Severe congenital non-autoimmune hyperthyroidism associated to a mutation in the extracellular domain of thyrotropin receptor gene. Arq Bras Endocrinol Metab. 2012;56(8):513-8.
• 15. Secchi LAA, Mazzeu JF, Córdoba MS, Ferrari I, Ramos HE, Neves FAR. Transient neonatal hypothyroidism in a boy with unbalanced translocation t(8;16). Arq Bras Endocrinol Metab. 2012;56(8):564-9.
• 16. Geraldo MV, Fuziwara CS, Friguglieti CUM, Costa RB, Kulcsar MAV, Yamashita AS, et al. MicroRNAs miR-146-5p and let-7f as prognostic tools for aggressive papillary thyroid carcinoma: a case report. Arq Bras Endocrinol Metab. 2012;56(8):552-7.
• 17. Kasuki L, Colli LM, Elias PCL, de Castro M, Gadelha MR. Resistance to octreotide LAR in acromegalic patients with high SSTR2 expression: analysis of AIP expression. Arq Bras Endocrinol Metab. 2012;56(8):501-6.
• 18. Boguszewski CL, Fighera TM, Bornschein A, Marques FM, Dénes J, Rattenbery E, et al. Genetic studies in a coexistence of acromegaly, pheochromocytoma, gastrointestinal stromal tumor (GIST) and thyroid follicular adenoma. Arq Bras Endocrinol Metab. 2012;56(8):507-12.
• 19. Blom CB, Ceolin L, Romitti M, Siqueira D, Maia AL. The rare intracellular RET mutation p.Ser891Ala in an apparently sporadic medullary thyroid carcinoma: a case report and review of the literature. Arq Bras Endocrinol Metab. 2012;56(8):586-91.
• 20. Chang CV, Conde SJ, Luvizotto RAM, Nunes VS, Bonates MC, Felicio AC, et al. Oncogenic osteomalacia: loss of hypophosphatemia might be the key to avoid misdiagnosis. Arq Bras Endocrinol Metab. 2012;56(8):570-3.
• 21. Guaragna MS, Lutaif ACGB, Bittencourt VB, Piveta CSC, Soardi FC, Castro LCG, et al. Frasier syndrome: four new cases with unusual presentations. Arq Bras Endocrinol Metab. 2012;56(8):525-32.
• 22. de Lima EU, Soares IC, Danilovic DLS, Marui S. New mutation in the PTEN gene in a Brazilian patient with Cowden's syndrome. Arq Bras Endocrinol Metab. 2012;56(8):592-6.
• 23. Corrêa-Giannella ML, Freire DS, Cavaleiro AM, Fortes MAZ, Giorgi RR, Pereira MAA. Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene. Arq Bras Endocrinol Metab. 2012;56(8):485-9.
• 24. Guttmacher AE, Collins FS. Genomic medicine-a primer. N Engl J Med. 2002;347(19):1512-20.

Publication Dates

• Publication in this collection
  02 Jan 2013
• Date of issue
  Nov 2012