Case 2.12
Monica Fawzy in Plastic Surgery Vivas for the FRCS(Plast), 2023
You’ve mentioned the 6th, 7th, and 8th clefts – associated with Treacher Collins. What are their phenotypes?Cleft number 6 passes between the maxilla and zygoma and may be associated with a coloboma of the lateral lower eyelid.Cleft number 7 runs between the zygoma and the temporal bone. It may extend medially across the cheek into the lateral aspect of the mouth – and may result in macrostomia.Cleft number 8 passes outwards from above the lateral canthus. It extends between the zygoma and the temporal bone into the greater wing of the sphenoid.
Genomic technologies
Wendy A. Rogers, Jackie Leach Scully, Stacy M. Carter, Vikki A. Entwistle, Catherine Mills in The Routledge Handbook of Feminist Bioethics, 2022
One of the central goals in medical genomics is to understand the relationship between genotype (i.e. an individual’s collection of genes) and phenotype (i.e. an individual’s observable characteristics or traits). DNA sequencing, computation analysis and information technologies are essential tools for studying genomes and understanding these relationships. The power of these technologies has increased in outstanding ways in the last decade. The initial draft of the human genome took around 15 months to complete and cost around USD 300 million (Lander et al. 2001). The advent of next-generation sequencing (NGS) technologies now permits an unprecedented DNA sequencing throughput and speed at significant cost reduction (van Dijk et al. 2018). A draft of a human genome can now be produced in about one day for a few thousand US dollars. NGS technologies are able to perform sequencing of millions of small fragments of DNA in parallel (Levy and Boone 2019). NGS platforms can be used to sequence nearly all DNA of a given organism, i.e. whole genome sequencing (WGS), or the DNA parts that code for proteins, i.e. whole-exome sequencing (WES). These technologies can also sequence selected genes or fragments of a genome-related to a set of disorders, i.e. targeted sequencing. Using sophisticated computational algorithms, these DNA sequences are then reconstructed into the original genome or are mapped to a reference genome for analysis.
Osteoarthritis
Nicole M. Farmer, Andres Victor Ardisson Korat in Cooking for Health and Disease Prevention, 2022
The epidemiology of OA is related to an array of person-level and disease-level factors. Person-level factors related to OA are age, obesity status, and race/ethnicity, and systemic risk factors such as hyperlipidemia or metabolic syndrome. In contrast, disease-level factors are related to disease phenotype, as well as joint or localized risk factors such as prior injury or leg muscle weakness. Overall, in the U.S., it is estimated that about 14 million Americans have symptomatic OA, with about half having advanced disease. More than half of these cases present in individuals who are less than 65 years of age (Deshpande et al., 2016). Thus, many of these patients with symptomatic OA will foreseeably deal with decades of treatment and management requirements. The rising prevalence of obesity plays a significant role in the prevalence of OA, especially with respect to certain disease phenotypes (Deveza et al., 2017). Worldwide estimates for prevalence of OA vary by country and region. For instance, prevalence among adults in India is 28.7% (Prakash et al., 2016), 16.9% in Iran (Davatchi et al., 2016), and 64.9% in South Korea (Lee and Kim, 2017).
A case of KAT6A syndrome with a newly discovered mutation in the KAT6A gene, mainly manifested as bone marrow failure syndrome
Published in Hematology, 2023
Qi Ai, Lihua Jiang, Yun Chen, Xiuyun Yao, Jing Yin, Sen Chen
We report the case of a child with KAT6A syndrome who had a de novo mutation, representing a new variant that has not been previously reported. The nonsense mutation occurs in exon 17 and causes proteins to have a truncated C-terminus, which in turn affects their function. Global developmental delay is a clinical presentation in almost all patients with KAT6A syndrome; it occurs early in life and is commonly the most prominent chief complaint. In the present case, the linguistic and intellectual development of the child was behind that of same-age children since before one year of age, and there was no change in muscle tone. These clinical manifestations were all classical clinical phenotypes reported in the literature, further confirming that this newly identified mutation expands the mutational spectrum of KAT6A syndrome. Therefore, studies on the correlation between genotypes and clinical phenotypes are of particular importance.
Candida auris biofilm: a review on model to mechanism conservation
Published in Expert Review of Anti-infective Therapy, 2023
Arsha Khari, Biswambhar Biswas, Garima Gangwar, Anil Thakur, Rekha Puria
Though one study revealed similar levels of virulence in C. auris and C. albicans, another found the non-aggregating phenotype to be considerably more pathogenic than C. albicans. Interestingly, recently C. auris was shown to be less pathogenic in a neutropenic murine bloodstream infection model than C. albicans [27,30]. Aggregative strains of C. auris produce more biofilm than non-aggregative ones. In contrast, Sherry et al. found that non-aggregating isolates of C. auris have a stronger biofilm-forming potential than aggregating isolates in Galleria mellonella larvae at 30°C and 37°C [27,31]. The ability of C. auris to form cellular aggregates improves yeast viability, which is linked with the activation of biofilm-related genes [16]. In the colonising group, non-aggregative isolates were less susceptible to amphotericin B and fluconazole than aggregative isolates [28]. The exact molecular mechanism responsible for these behaviours is not known. There is no unique answer to which phenotypes results in what? Can one strain under different stress conditions exhibit both phenotypes? Can phenotypes switch? Can phenotype help in the development of more therapeutic alternatives? Are phenotypes evolutionarily related?? More studies are required to precisely address the role of aggregation/non-aggregation behaviour in the pathogenicity of C. auris.
Outer retinal tubulations in maternally inherited diabetes & deafness – associated macular dystrophy: case report
Published in Ophthalmic Genetics, 2020
Maria Syriga, Vasileios Soumplis, Charalampos Kapernopoulos, Dimitris Kleftogiannis, Michael Karampelas
MIDD is a rare entity, frequently under- or misdiagnosed by physicians. History of diabetes along with hearing impairment and typical findings in fundoscopic examination should prompt further investigations for this disease. Previous molecular studies have revealed that the most frequent mutation is a substitution of an A to G at position 3243 of the mitochondrial DNA (m.3243A>G) encoding the gene for tRNALeu is the most common cause of MIDD (6,7). A strong family history with the transmission of the mutated mitochondrial DNA from the mother to all the descendants may also contribute to the accurate diagnosis. Although the molecular basis and the inheritance pattern are well characterized, the phenotype may present large variations among family members. The heterogeneity of MIDD is attributed to the different amount of mutated mitochondrial DNA in each tissue and the variable degree of inheritance from the mother to each descendant. This phenomenon is referred as heteroplasmy and therefore clinical manifestations and severity may vary from one subject to another, even in close family members (12). Therefore, the proper diagnosis of this entity should be followed by careful family screening and genetic counseling for the identification of more relatives carrying the mutation and should also include referral to other corresponding specialties for the management of associated comorbidities, despite the different phenotypes of each family member (13).
Related Knowledge Centers
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