Whole exome sequencing in 18 Brazilian families with vertical transmission of non-syndromic oral clefts.

This study describes the results of whole exome sequencing in the etiological investigation and genetic counseling of families presenting with non-syndromic oral clefts with vertical transmission recorded in the Brazilian Database on Craniofacial Anomalies. Whole exome sequencing was performed in 18 families presenting with non-syndromic oral clefts with vertical transmission, and variant filtering was used to identify rare, and also possibly pathogenic variants in genes associated with oral clefts. Overall, our study identified seven families (38.

Access to genetic evaluation of 1463 individuals with orofacial cleft in Brazil.

Objective: The current study delves into the accessibility of genetic evaluations for individuals with orofacial clefts (OC), comparing data between genetics and treatment centers across Brazil.

Methods: This cross-sectional retrospective study analyzed primary data from 1463 OC individuals registered in the Brazilian Database of Craniofacial Anomalies (BDCA) between 2008 and 2018 without age or sex selection. Diagnostic exam results stemming from research projects until 2023 were considered.

22q11.2 Deletion Syndrome: Influence of Parental Origin on Clinical Heterogeneity.

22q11.2 deletion syndrome (22q11.2DS) shows significant clinical heterogeneity.

Molecular investigation in individuals with orofacial clefts and microphthalmia-anophthalmia-coloboma spectrum.

This study describes genomic findings among individuals with both orofacial clefts (OC) and microphthalmia/anophthalmia/coloboma (MAC) recorded in the Brazilian Database on Craniofacial Anomalies (BDCA). Chromosomal microarray analysis (CMA) and Whole Exome Sequencing (WES) were performed in 17 individuals with OC-MAC. Clinical interpretation of molecular findings was based on data available at the BDCA and on re-examination.

Overlapping Spectrum of Craniofacial Microsomia Phenotype in Cat-Eye Syndrome.

This study reports three patients with Cat-eye Syndrome (CES), two of which present a previous clinical diagnosis of Craniofacial microsomia (CFM). Chromosomal microarray analysis (CMA) revealed a tetrasomy of 1,7 Mb at the 22q11.2q11.

So, and if it is not congenital adrenal hyperplasia? Addressing an undiagnosed case of genital ambiguity.

Background: The Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency is the most common cause of genital ambiguity in persons with XX sexual chromosomes. Genital ambiguity among persons with XY sexual chromosomes comprises diverse and rare etiologies. The deficiency of 17-beta-hydroxysteroid dehydrogenase type 3 enzyme (HSD17B3) is a rare autosomal recessive disorder due to functionally altered variants of the HSD17B3 gene.

Craniofacial microsomia: Reflections on diagnosis and severity assessment based on a series of cases.

This study aims to discuss diagnostic criteria and severity assessment for craniofacial microsomia (CFM). A series of 61 patients with diverse CFM phenotypes had their clinical data collected by experienced dysmorphologists using a single protocol. Genetic abnormalities were searched through karyotype and chromosomal microarray analysis.

Genomic imbalances in craniofacial microsomia.

The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist.

Brazil's Craniofacial Project: Different approaches on orofacial clefts and 22q11.2 deletion syndrome.

This article reports the present situation of Brazilian health care in genetics for Orofacial Cleft (OFC) and 22q11.2 Deletions Syndrome (22q11.2 DS) based on research conducted by Brazil's Craniofacial Project (BCFP).

Identification of genomic imbalances in oral clefts.

Objective: This article presents a clinical and cytogenomic approach that focuses on the diagnosis of syndromic oral clefts (OCs).

Methods: The inclusion criteria were individuals with OC presenting four or more minor signs and no major defects (non-syndromic oral clefts [NSOCs]) as well as individuals with OC presenting at least another major defect, regardless of the number of minor signs (syndromic oral clefts [SOCs]). The exclusion criteria included NSOC with less than four minor signs, SOC with known etiology, as well as atypical oral clefts.

An invincible memory: what surname analysis tells us about history, health and population medical genetics in the Brazilian Northeast.

Several studies have shown that the Brazilian Northeast is a region with high rates of inbreeding as well as a high incidence of autosomal recessive diseases. The elaboration of public health policies focused on the epidemiological surveillance of congenital anomalies and rare genetic diseases in this region is urgently needed. However, the vast territory, socio-demographic heterogeneity, economic difficulties and low number of professionals with expertise in medical genetics make strategic planning a challenging task.

Syndromic Oral Clefts: Challenges of Genetic Assessment in Brazil and Suggestions to Improve Health Policies.

Addressing the unmet health needs of persons living with congenital anomalies in low- and middle-income countries (LMIC) is a major challenge. Registries and databases are exemplary tools capable to link research data with health programs. Since 2009, Brazil's Craniofacial Project, a multicenter and voluntary research initiative, collects socioeconomic, medical, and genetic information on individuals with craniofacial anomalies through the Brazilian Database on Craniofacial Anomalies (BDCA).

Functional characterization of five NR5A1 gene mutations found in patients with 46,XY disorders of sex development.

Steroidogenic factor-1 (SF1), encoded by the NR5A1 gene, is a key regulator of steroidogenesis and reproductive development. NR5A1 mutations described in 46,XY patients with disorders of sex development (DSD) can be associated with a range of conditions of phenotypes; however, the genotype-phenotype correlation remains elusive in many cases. In the present study, we describe the impact of five NR5A1 variants (three novel: p.

CranFlow: An Application for Record-Taking and Management Through the Brazilian Database on Craniofacial Anomalies.

Background: The World Health Organization has recognized the relevance of databases on craniofacial anomalies since . To date, there is no universal standard instrument/database focused on risk factors, clinical and genetic data collection, and follow-up that enables comparison between different populations and genotype-phenotype correlation. Although studies have shown that specific genes would impact outcomes, knowledge is not sufficient to subsidize cost-effectiveness strategies for diagnosis, surgical decision, and a multi-professional approach toward personalized medicine.

Study of IRF6 and 8q24 region in non-syndromic oral clefts in the Brazilian population.

Objectives: We investigated the association between non-syndromic oral cleft and variants in IRF6 (rs2235371 and rs642961) and 8q24 region (rs987525) according to the ancestry contribution of the Brazilian population.

Subjects And Methods: Subjects with oral cleft (CL, CLP, or CP) and their parents were selected from different geographic regions of Brazil. Polymorphisms were genotyped using a TaqMan assay and genomic ancestry was estimated using a panel of 48 INDEL polymorphisms.

Genotype-phenotype correlation of 16p13.3 terminal duplication and 22q13.33 deletion: Natural history of a patient and review of the literature.

This article reports a patient with a de novo ∼ 9.32 Mb duplication at 16p13.3 and a ∼ 71 Kb deletion at 22q13.

A multicentric association study between 39 genes and nonsyndromic cleft lip and palate in a Brazilian population.

Purpose: The aim of this study was to use the TaqMan OpenArray system to evaluate associations between 39 genes and the etiology of nonsyndromic cleft lip and palate (NSCLP) in a Brazilian population.

Material And Methods: This case-control association study was designed with 80.11% statistical power according to logistic regression (GPOWER software).

[Profile of patients with genitourinary anomalies treated in a clinical genetics service in the Brazilian unified health system].

Objective:: To describe the profile of patients with genitourinary abnormalities treated at a tertiary hospital genetics service.

Methods:: Cross-sectional study of 1068 medical records of patients treated between April/2008 and August/2014. A total of 115 cases suggestive of genitourinary anomalies were selected, regardless of age.

Diagnostic implications of associated defects in patients with typical orofacial clefts.

Objectives: To describe prevalence of associated defects and clinical-genetic characteristics of patients with typical orofacial clefts seen at a reference genetic service.

Methods: Descriptive study conducted between September of 2009 and July of 2014. Two experienced dysmorphologists personally collected and coded clinical data using a validated, standard multicenter protocol.

Investigation of genetic factors underlying typical orofacial clefts: mutational screening and copy number variation.

Typical orofacial clefts (OFCs) comprise cleft lip, cleft palate and cleft lip and palate. The complex etiology has been postulated to involve chromosome rearrangements, gene mutations and environmental factors. A group of genes including IRF6, FOXE1, GLI2, MSX2, SKI, SATB2, MSX1 and FGF has been implicated in the etiology of OFCs.

Clinical Features in Patients With 22q11.2 Deletion Syndrome Ascertained by Palatal Abnormalities.

Objectives: The aim of this study was to describe clinical features in subjects with palatal abnormalities and to assess the distribution of these features among those with and without 22q11.2 deletion.

Design: Descriptive cohort.

Risk factors and the prevention of oral clefts.

This article presents general aspects of risk factors and particularities of the management of individuals with oral clefts (OCs). A practical manual of prevention and management of this congenital defect was prepared based on a review of the literature and using data from Brazilian multicenter studies. Since OCs require efforts from all levels of healthcare, the data herein presented permits appropriate follow-up for affected individuals and their families.

Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia.

Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia.

Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients.

In this study, 103 unrelated South-American patients with mucopolysaccharidosis type II (MPS II) were investigated aiming at the identification of iduronate-2-sulfatase (IDS) disease causing mutations and the possibility of some insights on the genotype-phenotype correlation The strategy used for genotyping involved the identification of the previously reported inversion/disruption of the IDS gene by PCR and screening for other mutations by PCR/SSCP. The exons with altered mobility on SSCP were sequenced, as well as all the exons of patients with no SSCP alteration. By using this strategy, we were able to find the pathogenic mutation in all patients.

Implementing the brazilian database on orofacial clefts.

Background. High-quality clinical and genetic descriptions are crucial to improve knowledge of orofacial clefts and support specific healthcare polices. The objective of this study is to discuss the potential and perspectives of the Brazilian Database on Orofacial Clefts.