Novel MYT1 variants expose the complexity of oculo-auriculo-vertebral spectrum genetic mechanisms.

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder characterized by anomalies mainly involving the structures derived from the first and second pharyngeal arches. The spectrum presents with heterogeneous clinical features and complex etiology with genetic factors not yet completely understood. To date, MYT1 is the most important gene unambiguously associated with the spectrum and with functional data confirmation. In this work, we aimed to identify new single nucleotide variants (SNVs) affecting MYT1 in a cohort of 73 Brazilian patients diagnosed with OAVS. In addition, we investigated copy number variations (CNVs) encompassing this gene or its cis-regulatory elements and compared the frequency of these events in patients versus a cohort of 455 Brazilian control individuals. A new SNV, predicted as likely deleterious, was identified in five unrelated patients with OAVS. All five patients presented hearing impairment and orbital asymmetry suggesting an association with the variant. CNVs near MYT1, located in its neighboring topologically associating domain (TAD), were found to be enriched in patients when compared to controls, indicating a possible involvement of this region with OAVS pathogenicity. Our findings highlight the genetic complexity of the spectrum that seems to involve more than one variant type and inheritance patterns.

Citrobacter freundii impairs the phosphoryl transfer network in the gills of Rhamdia quelen: Impairment of bioenergetics homeostasis.

The precise coupling of spatially separated intracellular adenosine triphosphate (ATP)-producing and ATP-consuming, catalyzed by creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), is a critical process in the bioenergetics of tissues with high energy demand, such as the branchial tissue. The effects of Citrobacter freundii infection on gills remain poorly understood, limited only to histopathological studies. Thus, the aim of this study was to evaluate whether experimental infection by C. freundii impairs the enzymes of the phosphoryl transfer network in gills of silver catfish (Rhamdia quelen). The CK (cytosolic and mitochondrial) and AK activities decreased in infected compared to uninfected animals, while the PK activity did not differ between groups. The gill histopathology of infected animals revealed extensive degeneration with fusion and necrosis of secondary lamellae, detachment of superficial epithelium, aneurysm, vessel congestion and inflammatory process. Based on these evidences, the inhibition and absence of an efficient communication between CK compartments caused the impairment of the branchial bioenergetics homeostasis, which was not compensated by the augmentation on branchial AK activity in an attempt to restore energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to branchial tissue in animals infected with C. freundii.

Frontonasal dysgenesis, first branchial arch anomalies, and pericallosal lipoma: A new subtype of frontonasal dysgenesis.

We report on two unrelated Brazilian boys with craniofacial anomalies that involve the frontonasal process and the first branchial arch associated with pericallosal lipoma. To our knowledge this condition seems to have been reported only once previously, but may represent a new condition within the group of the frontonasal dysgenesis. Clinical and imaging data, phenotypic evolution, and differential diagnosis are discussed.

Syndromes of the first and second pharyngeal arches: A review.

Our aim in this review is to discuss currently known mechanisms associated with three important syndromes of the first and second pharyngeal arches: Treacher Collins syndrome (TCS), Oculo-auriculo-vertebral syndrome (AOVS) and Auriculo-Condylar syndrome (ACS) or question mark ear syndrome. TCS and ACS are autosomal dominant diseases, with nearly complete penetrance and wide spectrum of clinical variability. The phenotype of the latter has several overlapping features with OAVS, but OAVS may exist in both sporadic and autosomal dominant forms. Mutations in the TCOF1 gene are predicted to cause premature termination codons, leading to haploinsuficiency of the protein treacle and causing TCS. Low amount of treacle leads ultimately to a reduction in the number of cranial neural crest cells migrating to the first and second pharyngeal arches. Other than TCS, the genes associated with ACS and OAVS are still unknown. The first locus for ACS was mapped by our group to 1p21-23 but there is genetic heretogeneity. Genetic heterogeneity is also present in OAVS. Based on the molecular analysis of balanced translocation in an OAVS patient, it has been suggested that abnormal expression of BAPX1 possibly due to epigenetic disregulation might be involved with the etiology of OAVS. Involvement of environmental events has also been linked to the causation of OAVS. Identification of factors leading to these disorders are important for a comprehensive delineation of the molecular pathways underlying the craniofacial development from the first and the second pharyngeal arches, for genetic counseling and to open alternative strategies for patient treatment.

Histopathological evidence of antagonistic effects of tributyltin on benzo[a]pyrene toxicity in the Arctic charr (Salvelinus alpinus).

We previously reported that long-term (54 days), repeated intraperitoneal exposure to low doses of tributyltin (TBT; 0.3 mg/kg) inhibited the metabolic activation of co-administered benzo[a]pyrene (BaP; 3 mg/kg) in the Arctic charr (Salvelinus alpinus); BaP, in turn, stimulated the metabolism and/or excretion of TBT. Here, we report the results of histopathological examinations of liver, kidney and pseudobranch tissue samples originating from these same fish. The results revealed higher lesion incidences at all sampling time points (Days 8, 32 and 56) among BaP-exposed fish compared with fish exposed to either TBT alone or combined with BaP. The severity of lesions like necrosis was also higher in BaP-exposed fish. Moreover, hepatic basophilic foci were observed exclusively in fish exposed to BaP alone. Together, these results provide new evidences that TBT can antagonize BaP toxicity in fish exposed to both pollutants under controlled laboratory conditions. In contrast, BaP does not appear to provide protection against TBT toxicity.

Utilización peroperatoria del azul de metileno en patología quística del segundo arco branquial / Preoperatory utilization of the methylence blue in cystic pathology of the branchial second arcus

Reportar la técnica de coloración con azul de metileno de lesiones derivadas de los arcos branquiales como un método que facilita su disección. Descripción de dos casos clínicos en pacientes jóvenes con patología cervical. La evaluación clínica y los estudios preoperatorios confirmaron el diagnóstico de quistes branquiales del segundo arco, quienes sometidas a resección quirúrgica previa infiltración de la lesión con azul de metileno, procediendo a la disección del cuello según técnica habitual. Se observa la lesión y sus límites perfectamente coloreados, delimitando sus relaciones con las estructuras vecinas. La evolución posoperatoria fue satisfactoria. Los quistes branquiales constituyen la patología tumoral congénita del cuello más frecuente. Es de suma importancia la adecuada disección de la lesión ya que sus relaciones con las estructuras profundas del cuello hacen probable la lesión iatrogénica. La utilización del colorante permitió la disección y resección más segura con menor riesgo de lesión. La literatura relacionada es revisada

Trago accesorio: estudio clínico-patológico de 16 casos / Accesory tragus: clinical-pathology study of 16 cases

Se presentan 16 casos de trago accesorio unilateral y solitario, con predominio en el sexo femenino y edad variable de aparición. Esta entidad poco sospechosa puede con su localización preauricular plantear numerosos diagnmósticos diferenciales. Se describen sus características histopatológicas y tratamiento

Trago accesorio: estudio clínico-patológico de 16 casos / Accesory tragus: clinical-pathology study of 16 cases

Se presentan 16 casos de trago accesorio unilateral y solitario, con predominio en el sexo femenino y edad variable de aparición. Esta entidad poco sospechosa puede con su localización preauricular plantear numerosos diagnmósticos diferenciales. Se describen sus características histopatológicas y tratamiento (AU)

Thyroglossal duct and second branchial cleft anomalies in adults.

Definitive treatment is surgical removal of the cyst and any tract, with care taken to preserve vital structures. TDCs and BCCs are congenital cervical lesions that are encountered in adults. Experiences at the Eye and Ear Hospital of Pittsburgh are reviewed. Forty-five patients with TDCs and 59 patients with BCCs were treated between 1983 and 1988. Clinical findings are discussed and principles for diagnosis are detailed.

Síndrome do primeiro e segundo arcos branquiais: caso clinico / First and second branchial arch syndrome: a case report

A síndrome do primeiro e segundo arcos branquiais é um distúrbio de desenvolvimento representado por hipoplasia unilateral das estruturas derivadas destes arcos branquiais. É apresentado um caso clínico desta síndrome, sendo as malformaçöes da mandíbula, da articulaçäo temporomandibular e de tecidos moles comparadas com os relatos da literatura. A importância do conhecimento desta entidade, bem como os aspectos preventivos da mesma, säo considerados

Manifestaciones dermatologicas de patologías branquiales: I. Parte / Dermatologic manifestations of branchial pathologies: I Part

Luego de una breve reseña embriológica de la formación de los arcos branquiales, se describen las características clínicas de las lesiones que en piel pueden ofrecer las mismas. El trago supernumerario se considera en su cuadro aislado y con las distintas combinaciones con que se puede presentar

Manifestaciones dermatológicas de patologías branquiales: II. Parte / Dermatologic manifestations of branchial pathologic: II Part

En la segunda parte de este trabajo se continúa con la descripción de anomalías en piel de las patologías de los arcos branquiales y se desarrollan las fístulas, sinus y quistes de ese origen, los que, junto a los tragos supernumerarios, ya comentados, se pueden presentar al dermatólogo para su diagnóstico y tratamiento

Manifestaciones dermatologicas de patologías branquiales: I. Parte / Dermatologic manifestations of branchial pathologies: I Part

Luego de una breve reseña embriológica de la formación de los arcos branquiales, se describen las características clínicas de las lesiones que en piel pueden ofrecer las mismas. El trago supernumerario se considera en su cuadro aislado y con las distintas combinaciones con que se puede presentar (AU)

Manifestaciones dermatológicas de patologías branquiales: II. Parte / Dermatologic manifestations of branchial pathologic: II Part

En la segunda parte de este trabajo se continúa con la descripción de anomalías en piel de las patologías de los arcos branquiales y se desarrollan las fístulas, sinus y quistes de ese origen, los que, junto a los tragos supernumerarios, ya comentados, se pueden presentar al dermatólogo para su diagnóstico y tratamiento (AU)