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Evelise Brizola,1 Temis M Félix,2 Jay R Shapiro3 1Bone and Osteogenesis Imperfecta Department, Kennedy Krieger Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA; 2Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Osteoporosis and Metabolic Bone Disorders Center, Bethesda, MD, USAAbstract: Osteogenesis imperfecta (OI) is a rare, heritable systemic disorder of bone and connective tissue, which in almost 90% of cases is due to mutations affecting the normal synthesis of type I collagen. In 1979, four OI phenotypes were categorized which were inherited as autosomal dominant characteristics. Individuals with OI present both genetic and phenotypic variabilities. Major characteristics of OI are bone fragility, blue sclerae, dentinogenesis imperfecta, short stature, scoliosis, and joint hyperextensibility. Both autosomal dominant and recessive inheritance are now recognized. Advances in molecular diagnosis have led to a major expansion in our understanding of the genetic basis for different OI phenotypes. To date, sequence variants in 17 genes are described as causative of OI. These genes regulate the synthesis of type I collagen pro-alpha polypeptide chains, proteins involved in type I collagen processing in the endoplasmic reticulum and proteins involved in osteoblast function. These new genetic associations have also led to uncertainty with regard to the current classification of OI phenotypes. Bisphosphonates have been widely used to improve bone mass and decrease fractures in both children and adults with OI. While effective in many but not all children when administered for 2–4 years, bisphosphonates have not proven effective in adults with OI. Studies are limited for treatment of adults with teriparatide and denosumab. Advances have been reported in the surgical management of OI. Although the role of physical therapy in the management of children and adults was previously described, this important treatment modality is significantly underutilized. Keywords: osteogenesis imperfecta, sequence variants, collagen, bisphosphonates, bone, treatment

Background: Osteogenesis imperfecta (OI) is a group of genetic disorders of collagen biosynthesis, characterized by low bone density leading to fractures. Most patients exhibit functional impairment and require the aid of a caregiver. The aim of this study is to assess the quality of life (QoL) of caregivers of patients with OI. Methods: In this cross-sectional study, a convenience sampling strategy was used to enroll adult caregivers of children and adolescents with OI who attended a referral center in southern Brazil. The WHOQOL-BREF instrument was used to assess QoL. Results: Twenty-four caregivers of 27 patients (10 with type I, 4 with type III, and 13 with type IV OI) were included in the study. Eighteen caregivers were the patients’ mothers, two had OI, and 22 cared for only one patient. Mean WHOQOL-BREF scores were 14.59 for the physical health domain, 13.80 for the psychological domain, 15.19 for the social relationships domain, and 12.87 for the environmental domain; the mean total QoL score was 14.16. QoL scores did not differ significantly according to patients’ OI type or number of fractures. Economic status was not correlated significantly with QoL scores. Conclusions: QoL appears to be impaired in caregivers of patients with OI. Additional studies are required to confirm these findings and to ascertain which factors account for this phenomenon.

Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion: The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct human neurogenetic disorders; however, a clinical overlap between AS and PWS has been identified. We report on a further case of a patient showing the PWS phenotype with the AS molecular defect. Despite the PWS phenotype, the DNA methylation analysis of SNRPN revealed an AS pattern. Cytogenetic and FISH analysis showed normal chromosomes 15 and microsatellite analysis showed heterozygous loci inside and outside the 15q11-13 region. The presence of these atypical cases could be more frequent than previously expected and we reinforce that the DNA methylation analysis is important for the correct diagnosis of severe mental deficiency, congenital hypotonia and obesity. A síndrome de Angelman (SA) e a síndrome de Prader-Willi (SPW) são doenças neurogenéticas distintas; entretanto, já foi observada sobreposição clínica entre essas duas patologias. Descrevemos mais um caso de um paciente apresentando o fenótipo da SPW e exames moleculares compatíveis com a SA. Apesar do fenótipo da SPW, o teste da metilação do DNA no gene SNRPN revelou padrão compatível com a SA. A análise citogenética e análise por FISH mostraram ambos os cromossomos 15 normais e a análise de polimorfismo de microssatélite mostrou heterozigozidade para marcadores dentro e fora da região 15q11-13. A presença destes casos atípicos pode ser mais freqüente que o esperado e salientamos que a análise da metilação do DNA é importante para o diagnóstico correto de deficiência mental, hipotonia congênita e obesidade.

Os defeitos de fechamento de tubo neural constituem uma das malformações mais freqüentes na espécie humana, apresentando alta morbi-mortalidade. Sua etiologia é considerada multifatorial, estando envolvidos fatores genéticos e ambientais. Estes fatores estão relacionados principalmente com o metabolismo da homocisteína. Realizamos um estudo de caso-controle com o objetivo de estudar os fatores bioquímicos e genéticos relacionados ao DTN na nossa população. Em pares de afetados com DTN e suas mães e pares de pacientes normais e suas mães foram avaliados dosagem de folato, vitamina B12, homocisteína e polimorfismos da enzima metileno tetraidrofolato redutase (MTHFR), C677T e A1298C. A dosagem de folato nos casos foi 11,37 ng/mL(±6,72) e nos controles 5,64 ng/mL(±4,16) (p

Mulheres com cariótipo XY e gônadas em fita são consideradas portadoras de disgenesia gonadal. Essas pacientes apresentam um risco mais alto de desenvolver doenças nas gônadas. Em tais casos, a remoção cirúrgica profilática é indicada. Este artigo relata o caso de uma paciente com disgenesia, apresentando cariótipo 45,X/46,XY. Foi realizada ressecção profilática das gônadas através de laparoscopia. A laparoscopia tem um papel importante na exploração de estruturas pélvicas e permite o diagnóstico, o prognóstico e o tratamento de lesões. Além disso, oferece um método efetivo para a gonadectomia. A remoção profilática das gônadas disgenéticas utilizando essa técnica cirúrgica tem sido preferida em pacientes selecionados. Females with XY karyotype and streak gonads are classified as presenting XY gonadal dysgenesis. These patients are at higher risk of developing malignancy in their gonads; in such cases prophylactic surgical removal is indicated. This article reports a case in which a patient with dysgenesis presented 45,X/46,XY karyotype. Laparoscopic prophylactic gonadal resection was performed. Laparoscopy plays an important role in exploring pelvic structures and allows the diagnosis, prognosis and treatment of lesions. In addition, it provides an effective method for gonadectomy. The prophylactic removal of dysgenetic gonads using this surgical technique has been preferred in selected patients lately.

INTRODUÇÃO: Retardo mental está presente em aproximadamente 2-3% da população. Geneticistas clínicos são chamados freqüentemente para avaliar crianças com atraso no de senvolvimento neuropsicomotor ou deficiência mental. A identificação da causa da deficiência mental irá beneficiar o indivíduo e famílias, respondendo questões sobre manejo, prognóstico, risco de recorrência e prevenção. MATERIAL E MÉTODOS: Análise genético-clínica numa população de 260 deficientes men tais de uma instituição é apresentada. RESULTADOS: Os 260 pacientes distribuíram-se numa razão de 1.3 do sexo masculino para 1 do sexo feminino. A idade variou de 1 mês a 47 anos com a mediana de 5 anos e um mês. Usando dados pessoais e familiares, exame físico detalhado e investigação laboratorial, os autores estabeleceram diagnóstico definitivo em 171 pacientes (65,76%). Alterações constitucionais estavam presentes em 147 pacientes (56,53%). CONCLUSÃO: Pacientes com Síndrome de Down representaram 32,20% e 3,84% apresentaram anomalias envolvendo outros cromossomos, incluindo síndromes de microdeleção. Em 32 pacientes (12,30%) uma doença mendeliana foi diagnosticada. Em 11 pacientes (4,23%) uma anomalia congênita múltipla/retardo mental (ACM/RM) foi diagnosticada. Dez pacientes (3,84%) apresentaram uma malformação do sistema nervoso central (SNC). Uma condição adquirida foi observada em 26 pacientes (10%), representando 7,69% de disfunção do SNC, 2,3% de infecção pre ou pós-natal e 0,4% de dano pós-natal, excluindo infecções. Em 87 pacientes (34,46%) não foi possível determinar um diagnóstico. INTRODUCTION: Mental retardation is present in approximately 2-3 % of the population. Clinical geneticists are frequently asked to evaluate children with development delay or mental retardation. Identifying the cause of the mental retardation will benefit individuals and families, answering questions about management, prognosis, recurrence risks and prevention. MATERIAL AND METHODS: A genetic diagnostic survey in a population of 260 mentally retarded institutionalized patients in the South of Brazil is presented. RESULTS: The patients had a male:female ratio of 1.3:1 and their ages varied from 1 month to 47 years with a mean of 5 years and one month. Using personal and family data, careful clinical examination and laboratory investigation, the authors established a definitive diagnosis in 171 patients (65.76%). A constitutional disorder was present in 147 patients (56.53%). CONCLUSION: Down syndrome patients represented 32.30% and 3,84% had other chromosomal anomalies, including microdeletion syndromes. In 32 patients (12.30%) a mendelian inheritance disorder was diagnosed. In eleven patients (4.23%) a MCA/MR syndrome was recorded. Ten patients (3.84%) presented a CNS malformation. An acquired condition was observed in 26 patients (10%), representing 7.69 % of CNS dysfunction, 2.3% of pre- or postnatal infection and 0.4% of postnatally acquired conditions other than infections. In the remaining 87 patients (34.46%) a conclusive diagnosis was not possible.

É sabido que a otite média aguda pode ser causada por fatores ambientais, comofreqüentar creches, fumo passivo, curto período de amamentação e baixas condições sócio-eco-nômicas. A revisão das pesquisas recentes, contudo, sugere que fatores genéticos também contri-buem de forma significativa para a ocorrência da otite média aguda, recorrente e da otite médiacrônica, com efusão. Embora não existam estudos genéticos específicos, há consistentes evidên-cias em favor da transmissão genética de uma suscetibilidade para otite média. A história familiar,características raciais, a freqüência de antígenos HLA e de marcadores genéticos, entre outrosfatores, são algumas das evidências que serão apresentadas nesta revisão de literatura. It is well-known that otitis media can be caused by environmental factors, such asattending day care centers, passive smoking, early interruption of breast feeding, and unfavorablesocio-economic conditions. The review of current literature, however, suggests that genetic factorsalso contribute significantly to the occurrence of recurrent acute otitis media and otitis media witheffusion. Although there are no specific genetic studies, there is consistent evidence to support theidea of genetically transmitted susceptibility to otitis media. Family history, racial characteristics,HLA and genetic marker frequency are some of the topics discussed in the literature, which will bepresented in this review.

Background Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted. Methods/design This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings. Discussion The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women. ClinicalTrials.gov Identifier NCT00397917

Introdução: Osteogênese imperfeita (OI) é uma doença do colágeno com manifestações clínicas ósseas e extraósseas. Entre as características extraósseas, estão descritas alterações no sistema estomatognático. Objetivo: Caracterizar aspectos morfofuncionais e eletrofisiológicos do sistema estomatognático em crianças e adolescentes com diagnóstico de OI. Métodos: Estudo transversal com 22 participantes, divididos nos grupos OI Leve (OIL) (tipo 1) (n=15) e OI Moderada-Grave (OIMG) (tipos 3, 4 e 5) (n=7). Foram realizadas avaliações clínicas odontológicas. Aplicou-se o protocolo Avaliação Miofuncional Orofacial com Escores (AMIOFE) para avaliar os aspectos miofuncionais orofaciais. A atividade elétrica dos músculos masseter, temporal anterior e da região supra-hioidea foi avaliada por eletromiografia de superfície durante repouso e as tarefas de contração voluntária máxima (máxima intercuspidação), mastigação, deglutição incompleta de saliva, deglutição de líquido com volume confortável e deglutição de saliva. O Iowa Oral Pressure Instrument (IOPI) foi utilizado para medir a pressão da língua em diferentes tarefas. Resultados: Dentição permanente foi observada em 61,1% dos participantes e dentinogênese imperfeita em 15,8%. Com relação aos aspectos miofuncionais orofaciais, alteração da postura de lábios e língua foi observada em 54,5%, do aspecto das bochechas em 59,1% e da face em 72,7%. Na deglutição, 40,9% apresentaram alteração labial e 59,1% de língua. O padrão mastigatório unilateral preferencial foi observado em 54,5%. O escore total no AMIOFE foi 90,86 pontos na amostra total, 91,71 no OIL e 89,14 no OIMG. O padrão mastigatório não influenciou a ativação elétrica nas tarefas de máxima intercuspidaçao e mastigação. Nos índices de ativação muscular, os grupos diferiram estatisticamente em todas as tarefas avaliadas, p = 0,046 para repouso, p = 0,014 para máxima intercuspidação, p = 0,005 para mastigação livre, p = 0,001 para mastigação direcionada à direita e p = 0,012 para mastigação direcionada à esquerda, indicando predomínio de uso da musculatura massetérica no grupo OIMG e de temporal anterior no grupo OIL em todas as tarefas avaliadas. Na deglutição de líquido contínuo (100mL), OIMG apresenta para masseter direito (p = 0,026) e esquerdo (p = 0,038) maior percentual de ativação do que OIL. Quanto maior o escore para o comportamento dos lábios durante a deglutição, menor a ativação elétrica da região supra-hioidea durante repouso (p = 0,026). Com relação à pressão de língua, a amostra total apresentou a pressão anterior de língua de 49kPa, 52kPa o grupo OIL e 42,57kPa o grupo OIMG. A pressão da região anterior durante deglutição de saliva na amostra total foi 23kPa, no grupo OIL foi 23,64kPa e no grupo OIMG foi 21,71kPa. A pressão da região posterior na amostra total foi 47,82kPa, enquanto no grupo OIL foi 52,80kPa e no grupo OIMG foi 37,14kPa. Verificou-se que elevada pressão anterior de língua está correlacionada à elevada pressão posterior (p = 0,001). Entre os grupos de OI, foi observada maior pressão de língua da região posterior no grupo OIL (p = 0,007). Conclusões: A condição miofuncional orofacial não foi estatisticamente diferente de acordo com a gravidade da OI em crianças e adolescentes, embora OIMG apresentou menor escore total no protocolo AMIOFE e, em geral, mais alterações dentárias. A ativação dos músculos supra-hioideos durante deglutição de saliva e líquido contínuo foram semelhantes entre os grupos. A ativação dos músculos masseteres foi superior no grupo OIMG nas tarefas de repouso, deglutição de saliva, deglutição de volume confortável e deglutição contínua, indicando maior necessidade de manter a estabilização mandibular durante estas tarefas no grupo OIMG. Para o total da amostra maior pressão da região anterior de língua correlaciona-se à maior pressão da região posterior de língua. Introduction: Osteogenesis imperfecta (OI) is a collagen disorder with several clinical bone and extra-bone findings. Among the extra-bone characteristics, alterations in the stomatognathic system are described. Objective: To characterize morphofunctional and electrophysiological aspects of the stomatognathic system in children and adolescents diagnosed with OI. Methods: A cross-sectional study with 22 participants, divided into groups: Mild OI (MOI) (type 1) (n=15) and Moderate-to-Severe OI (MSOI) (types 3, 4 and 5) (n=7). Dental clinical evaluations were performed. The Orofacial Myofunctional Assessment with Scores (OMES) protocol was applied to assess orofacial myofunctional aspects. The electrical activity of the masseter, anterior temporal and suprahyoid muscles was evaluated by surface electromyography during rest and the tasks of maximal voluntary contraction (maximum intercuspation), mastication, incomplete swallowing of saliva, swallowing of liquid with comfortable volume and swallowing. of saliva. The Iowa Oral Pressure Instrument (IOPI) was used to measure tongue pressure on different tasks. Results: Permanent dentition was observed in 61.1% of the participants and dentinogenesis imperfecta in 15.8%. Regarding the orofacial myofunctional aspects, changes in the posture of lips and tongue were observed in 54.5%, in the appearance of the cheeks in 59.1% and in the face in 72.7%. In swallowing, 40.9% had labial alterations and 59.1% had tongue alterations. The preferential unilateral masticatory pattern was observed in 54.5%. The total score on OMES was 90.86 points in the total sample, 91.71 in the MOI and 89.14 in the MSOI. The masticatory pattern did not influence the electrical activation in the maximum intercuspation and chewing tasks. In muscle activation indices, the groups differed statistically in all evaluated tasks, p = 0.046 for rest, p = 0.014 for maximum intercuspation, p = 0.005 for free chewing, p = 0.001 for chewing directed to the right and p = 0.012 for directed chewing on the left, indicating predominance of use of the masseteric musculature in the MSOI group and of anterior temporal muscles in the MOI group in all evaluated tasks. In the swallowing of continuous liquid (100mL), MSOI presents a higher percentage of activation for the right (p = 0.026) and left (p = 0.038) masseter than MOI. The higher the score for the behavior of the lips during swallowing, the lower the electrical activation of the suprahyoid region during rest (p = 0.026). Regarding the tongue pressure, the total sample presented the anterior tongue pressure of 49kPa, 52kPa for the MOI group and 42.57kPa for the MSOI group. The pressure of the anterior region during saliva swallowing in the total sample was 23kPa, in the MOI group 23.64kPa and in the MSOI group 21.71kPa. The pressure of the posterior region in the total sample was 47.82kPa, in the MOI group 52.80kPa and in the MSOI group 37.14kPa. It was found that high anterior tongue pressure is correlated with high posterior pressure (p = 0.001). Among the OI groups, greater tongue pressure in the posterior region was observed in the MOI group (p = 0.007). Conclusions: The orofacial myofunctional condition was not statistically different according to the severity of OI in children and adolescents, although MSOI had a lower total score in the OMES protocol and, in general, more dental changes. Activation of the suprahyoid muscles during saliva and continuous liquid swallowing was similar between the groups. Activation of the masseter muscles was higher in the MSOI group in the tasks of rest, saliva swallowing, comfortable volume swallowing and continuous swallowing, indicating a greater need to maintain mandibular stabilization during these tasks in the MSOI group. In the total sample greater pressure in the anterior region of the tongue is correlated with greater pressure in the posterior region of the tongue.

Introdução: A osteogênese imperfeita é uma condição genética rara caracterizada principalmente pela fragilidade óssea. A maioria dos casos é causada por alteração nos genes que codificam o colágeno tipo 1, COL1A1 e COL1A2. Outros genes que participam das modificações pós-traducionais, enovelamento da tripla hélice, crosslink, mineralização, desenvolvimento ósseo, diferenciação e maturação celular também já foram relacionados com OI demonstrando a heterogeneidade genética desta condição. Objetivo: Realizar a caracterização molecular de osteogênese imperfeita no Brasil. Métodos: Os casos foram selecionados na Rede Brasileira de Osteogênese Imperfeita e dados clínicos coletados. A análise molecular foi realizada no equipamento Ion Torrent através de painel de NGS que cobre 99,6% da região de codificação de 18 genes para OI. Resultados: Foram incluídos 156 pacientes nas análises moleculares, variantes foram detectadas em 121 casos. Alterações nos genes COL1A1 e COL1A2 representam a maioria dos casos (88,4%), enquanto em 1,7% foram detectadas variantes em IFITM5 e em 9,9% em genes com padrão de herança recessiva: FKBP10 (4), CRTAP (1), P3H1 (3), PPIB (2), SERPINH1 (1) e TMEM38B (1). No total, 91 variantes diferentes foram identificadas, 25 consideradas novas. Das 65 variantes em COL1A1, 40 eram qualitativas e 25 quantitativas, e em COL1A2, 40 eram qualitativas e 2 quantitativas. A consanguinidade foi observada em 9 casos com variantes em COL1A1, COL1A2, CRTAP, FKBP10, SERPINH1 ou P3H1. Uma variante (c.179A>C; p.Gln60Pro) em FKBP10 foi detectada em 3 casos não relacionados residentes na Bahia; sugerindo um efeito fundador. Oito indivíduos, com variabilidade fenotípica, apresentam uma mesma variante em COL1A2 (c.2341G>A; p.Gly781Ser); 4 demonstram um tipo leve e 4 moderado. Dados clínicos foram coletados em 113 pacientes, 43 apresentaram fenótipo do tipo IV, enquanto 25 tipo I, 35 tipo III, 1 tipo II e 1 tipo V. Foi identificado um caso da variante c.119C>G (p.Ser40Trp) em IFITM5 que apresenta OI leve. História familiar positiva foi identificada em 36,5% dos casos, 92,03% tinham esclera azulada e 58% tinham dentinogênese imperfeita. Alterações quantitativas em COL1A1 e COL1A2 foram observadas em 24,5% da amostra e a maioria dos casos apresentavam OI leve. Em 75,5%, alterações qualitativas estavam associadas à OI moderada, grave ou letal; 49,3% desses casos apresentaram uma troca de glicina por serina. Conclusão: Como já relatado, a maioria dos casos se concentram nos genes COL1A1 e COL1A2. OI de causa autossômica recessiva foi identificada em 9% da amostra. Mais estudos são necessários para confirmar o efeito fundador nos casos da variante possivelmente fundadora em FKBP10. Dados desta grande coorte permitem compreender o fenótipo e o genótipo da OI no Brasil. Introduction: Osteogenesis imperfecta is a rare genetic condition mainly characterized by bone fragility. Most cases are caused by alteration in the genes that encode type 1 collagen, COL1A1 and COL1A2. Other genes that participate in post-translational modifications, triple helix folding, crosslink, mineralization, bone development, differentiation and cell maturation also play a role in OI, demonstrating the genetic heterogeneity of this condition. Objective: To perform molecular characterization of osteogenesis imperfecta in Brazil. Methods: Cases were selected at the Brazilian Osteogenesis Imperfecta Network and clinical data collected. Molecular analysis was performed in the Ion Torrent equipment through an NGS panel that covers 99.6% of the coding region of 18 genes for OI. Results: 156 patients were included in the molecular analyses, variants were detected in 121 cases. Alterations in COL1A1 and COL1A2 genes represent the majority of cases (88.4%), while variants were detected in IFITM5 in 1.7% and in 9.9% in genes with recessive inheritance pattern: FKBP10 (4), CRTAP (1), P3H1 (3), PPIB (2), SERPINH1 (1) and TMEM38B (1). In total, 91 different variants were identified, 26 of which were considered novel. Of the 65 variants in COL1A1, 40 were qualitative and 25 were quantitative, and in COL1A2, 40 were qualitative and 2 were quantitative. Consanguinity was observed in 9 cases with variants in COL1A1, COL1A2, CRTAP, FKBP10, SERPINH1 or P3H1. A variant (c.179A>C; p.Gln60Pro) in FKBP10 was detected in 3 unrelated cases residing in Bahia, suggesting a founder effect. Eight individuals, with phenotypic variability, present the same variant in COL1A2 (c.2341G>A; p.Gly781Ser): 4 demonstrate a mild type and 4 moderate. Clinical data were collected on 113 patients, 43 had a type IV phenotype, while 25 type I, 35 type III, 1 type II and 1 type V. One case of variant c.119C>G (p.Ser40Trp) was identified in IFITM5 with mild OI. A positive family history was identified in 36.5% of cases, 92.03% had blue sclera and 58% had dentinogenesis imperfecta. Quantitative changes in COL1A1 and COL1A2 were observed in 24.5% of the sample and most cases have mild OI. In 75.5%, qualitative changes were associated with moderate, severe, or lethal OI; 49.3% of these cases showed an exchange of glycine for serine. Conclusion: As already reported in the literature, most cases are concentrated in the COL1A1 and COL1A2 genes. OI of autosomal recessive inheritance was identified in 9% of the sample. More studies are needed to confirm the possible founder effect of the variant in FKBP10. Data from this large cohort allow us to understand the phenotype and genotype of OI in Brazil.