Siblings with Imperforate anus and aplastic nasal alae: Johanson-Blizzard syndrome

Johanson-Blizzard syndrome is a rare genetic entity reported in medical literature resulting from mutations in UBR1 gene, affecting pancreas, craniofacial and urogenital development, causing significant morbidity and mortality. We report a neonate presenting with anorectal malformation requiring surgical intervention at birth, with similar surgeries being performed in two elder siblings. Surviving sibling of the proband neonate also has similar dysmorphic features of absent ala nasi, aplasia cutis of scalp along with pancreatic insufficiency, profound sensorineural hearing loss, pheno-type corresponding to Johanson-Blizzard syndrome. Syndromic diagnosis helps in screening for associated potential issues, which can intervened at early stages.

ARID1A Variations in Cholangiocarcinoma: Clinical Significances and Molecular Mechanisms

Cholangiocarcinoma (CCA), a high mortality malignant carcinoma characterized by advanced disease and frequent recurrence, constitutes a major challenge for treatment and prognosis. AT-rich interaction domain 1A (ARID1A) variation is a distinct genetic entity in CCA, getting mounting concerns recently. Here, we comprehensively reviewed the clinical significance and molecular mechanisms of ARID1A alterations in CCA. Based on the independent data derived from 29 relevant studies, the variation rate of ARID1A in intrahepatic and extrahepatic CCA is reported at 6.9–68.2% and 5–55%, respectively. Most of the included studies (28/29, 96.6%) suggest that ARID1A serves as a tumor suppressor in CCA. ARID1A variation may be an important prognostic indicator to predict disease mortality, metastasis, and recurrence in patients with CCA. Multifactorial molecular mechanisms are involved in the relationship between ARID1A variations and the pathogenesis and pathophysiology of CCA, including disruption of the cell cycle, chromatin remodeling, oxidative stress damage, DNA hypermethylation, and the interaction of multiple genes being affected. This review describes that ARID1A variation might be a potential diagnostic and prognostic biomarker for CCA. Future diagnoses and treatments targeting ARID1A hint towards a precision medicine strategy in the management of CCA.

Pierquin Syndrome: Report of a New Case

Pierquin syndrome is a rare genetic entity characterized by the association of Dandy–Walker malformation and postaxial polydactyly. The incidence is uncertain with only six cases previously reported in the literature. In this study, we reported a new case of Pierquin syndrome born from consanguineous parents, characterized by Dandy–Walker malformation, postaxial polydactyly, and congenital heart disease. The case reinforces an autosomal recessive modality of inheritance and expands the phenotypic spectrum of this rare malformation syndrome.

Albinism in Didelphis virginiana (Kerr, 1792): the first reported case in Mexico

Atypical colorations occur in different groups of vertebrates. The loss of melanin in the skin, hair and eyes is the result of an autosomal recessive genetic entity. It causes individuals to present with a white coloration of the skin and hair, as well as red eyes, known as albino. This manuscript documents the first record in Mexico of complete albinism in a marsupial, Didelphis virginiana, captured in the Yucatan peninsula.

Genetic heterogeneity of cytogenetically normal AML with mutations of CEBPA

Biallelic mutations of the CCAAT/enhancer binding protein α (CEBPA) gene define a distinct genetic entity of acute myeloid leukemia (AML) with favorable prognosis. The presence of GATA2 and CSF3R mutations that are specifically associated with this subgroup but not mutated in all samples suggests a genetic heterogeneity of biCEBPA-mutated AML. We characterized the mutational landscape of CEBPA-mutated cytogenetically normal AML by targeted amplicon resequencing. We analyzed 48 biallelically mutated CEBPA (biCEBPA), 32 monoallelically mutated CEBPA (moCEBPA), and 287 wild-type CEBPA (wtCEBPA) patient samples from German AML Cooperative Group studies or registry. Targeted sequencing of 42 genes revealed that moCEBPA patients had significantly more additional mutations and additional mutated genes than biCEBPA patients. Within the group of biCEBPA patients, we identified 2 genetic subgroups defined by the presence or absence of mutations in chromatin/DNA modifiers (C), cohesin complex (C), and splicing (S) genes: biCEBPACCSpos (25/48 [52%]) and biCEBPACCSneg (23/48 [48%]). Equivalent subgroups were identified in 51 biCEBPA patients from the Cancer Genome Project. Patients in the biCEBPACCSpos group were significantly older and had poorer overall survival and lower complete remission rates following intensive chemotherapy regimens compared with patients in the biCEBPACCSneg group. Patients with available remission samples from the biCEBPACCSpos group cleared the biCEBPA mutations, but most had persisting CCS mutations in complete remission, suggesting the presence of a preleukemic clone. In conclusion, CCS mutations define a distinct biological subgroup of biCEBPA AML that might refine prognostic classification of AML. This trial was registered at www.clinicaltrials.gov as #NCT00266136 and NCT01382147.

Myocardial non-compaction

Isolated left ventricular non-compaction is a controversial entity which has only been reported in the past 30 years. It is becoming more frequently diagnosed due to the use of echocardiography and MRI. It can present in fetal life, infancy, childhood, and adult life. Clinically, the patient can present with cardiac arrhythmias, cardiac failure, systemic emboli due to thrombosis within the ventricles, and sudden death. It can be a genetic entity associated with mutations in many genes associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy. It is a rare entity found at autopsy and is more common in children than adults. In the past the prognosis has been considered worse in children then in adults. Treatment is usually empirical, dealing with the cardiac failure, arrhythmias, and thromboemboli.

Fungal taxonomy and nomenclature

This chapter summarizes historical and modern approaches to fungal taxonomy, the current taxonomic standing of medically important fungi, and the implications for fungal nomenclature following the recent Amsterdam Declaration on Fungal Nomenclature, which prohibits dual nomenclature. Fungi comprise an entire kingdom, containing an estimated 1–10 million species. Traditionally, fungal identification was based on examination of morphological and phenotypic features, including the type of sexual spores they form and method of formation, and structural features of their asexual spores. Thus, many fungi have been described and named independently several times, based on either their sexual or asexual stages, resulting in a single genetic entity having multiple names. Recent molecular approaches to fungal identification have led to profound changes in fungal nomenclature and taxonomy. Certain phyla have now been disbanded, cryptic species have been identified via molecular approaches, and long-recognized species have been transferred to new genera, based on genotypic comparisons.

Fungal taxonomy and nomenclature

This chapter summarizes historical and modern approaches to fungal taxonomy, the current taxonomic standing of medically important fungi, and the implications for fungal nomenclature following the recent Amsterdam Declaration on Fungal Nomenclature, which prohibits dual nomenclature. Fungi comprise an entire kingdom, containing an estimated 1–10 million species. Traditionally, fungal identification was based on examination of morphological and phenotypic features, including the type of sexual spores they form, and method of formation, and structural features of their asexual spores. Thus, many fungi have been described and named independently several times based on either their sexual or asexual stages, resulting in a single genetic entity having multiple names. Recent molecular approaches to fungal identification have led to profound changes in fungal nomenclature and taxonomy. Certain phyla have now been disbanded, cryptic species have been identified via molecular approaches, and long-recognized species have been transferred to new genera based on genotypic comparisons.