Clinical and genetic investigation of ichthyosis in familial and sporadic cases in south of Tunisia: genotype–phenotype correlation

Background Ichthyosis is a heterogeneous group of Mendelian cornification disorders that includes syndromic and non-syndromic forms. Autosomal Recessive Congenital Ichthyosis (ARCI) and Ichthyosis Linearis Circumflexa (ILC) belong to non-syndromic forms. Syndromic ichthyosis is rather a large group of heterogeneous diseases. Overlapping phenotypes and genotypes between these disorders is a major characteristic. Therefore, determining the specific genetic background for each form would be necessary. Methods A total of 11 Tunisian patients with non-syndromic (8 with ARCI and 2 with ILC) and autosomal syndromic ichthyosis (1 patient) were screened by a custom Agilent HaloPlex multi-gene panel and the segregation of causative mutations were analyzed in available family members. Results Clinical and molecular characterization, leading to genotype–phenotype correlation in 11 Tunisian patients was carried out. Overall, we identified 8 mutations in 5 genes. Thus, in patients with ARCI, we identified a novel (c.118T > C in NIPAL4) and 4 already reported mutations (c.534A > C in NIPAL4; c.788G > A and c.1042C > T in TGM1 and c.844C > T in CYP4F22). Yellowish severe keratoderma was found to be associated with NIPAL4 variations and brachydactyly to TGM1 mutations. Two novel variations (c.5898G > C and c.2855A > G in ABCA12) seemed to be features of ILC. Delexon13 in CERS3 was reported in a patient with syndromic ichthyosis. Conclusions Our study further extends the spectrum of mutations involved in ichthyosis as well as clinical features that could help directing genetic investigation.

Immunological and Genetic Investigation of SARS-CoV-2 Reinfection in an Otherwise Healthy, Young Marine Recruit

We used epidemiologic and viral genetic information to identify a case of likely reinfection in an otherwise healthy, young Marine recruit enrolled in the prospective, longitudinal COVID-19 Health Action Response for Marines (CHARM) study, and we paired these findings with serological studies. This participant had a positive RT-PCR to SARS-CoV-2 upon routine sampling on study day 7, although he was asymptomatic at that time. He cleared the infection within seven days. On study day 46, he had developed symptoms consistent with COVID-19 and tested positive by RT-PCR for SARS-CoV-2 again. Viral whole genome sequencing was conducted from nares swabs at multiple time points. The day 7 sample was determined to be lineage B.1.340, whereas both the day 46 and day 49 samples were B.1.1. The first positive result for anti-SARS-CoV-2 IgM serology was collected on day 49 and for IgG on day 91. This case appears most consistent with a reinfection event. Our investigation into this case is unique in that we compared sequence data from more than just paired specimens, and we also assayed for immune response after both the initial infection and the later reinfection. These data demonstrate that individuals who have experienced an infection with SARS-CoV-2 may fail to generate effective or long-lasting immunity, similar to endemic human beta coronaviruses.

Kahawai Phylogeny and Phylogenetics: A Genetic Investigation into Commercial and Recreational Fisheries Management and Practice

<p>Globally, commercially exploited fish species are coming under more and more pressure as the population of humans grow. Protein from the sea has traditionally been available to coastal communities throughout history. In modern times however, traditional artisanal fisheries have been replaced by commercial fishing industries. It is estimated by some authorities that these modern fisheries have led to decreases in pre-exploitation biomass of desirable species of up to 90%. As desirable species decline, secondary species become more valuable and subject to exploitation. An issue with this exploitation is that management decisions of fish stocks are often based on political or commercial concerns rather than sound science focussed on preserving stocks, and ultimately, fishing industries. To investigate phylogenetic and phylogeographic relationships of fish, kahawai (Arripis trutta) was used as a proxy species. A. trutta is one of only four members of the genus Arripis, which in turn is the sole member of the family Arripidae. It was found that a single, highly connected population of A. trutta inhabit New Zealand waters, and approximately 15 migrants per generation make the journey between New Zealand and Australia, genetically linking these populations. A phylogeny of A. trutta was resolved using mitochondrial DNA, and while COX1 data supported the hypothesis that A. trutta forms a monophyletic clade within the Stromateoids (medusa fish, squaretails and drift fish) and the Scombrids (tuna, mackerel and their allies) suggesting a common ancestor, other data collected during the investigation does not support this hypothesis.</p>

Kahawai Phylogeny and Phylogenetics: A Genetic Investigation into Commercial and Recreational Fisheries Management and Practice

<p>Globally, commercially exploited fish species are coming under more and more pressure as the population of humans grow. Protein from the sea has traditionally been available to coastal communities throughout history. In modern times however, traditional artisanal fisheries have been replaced by commercial fishing industries. It is estimated by some authorities that these modern fisheries have led to decreases in pre-exploitation biomass of desirable species of up to 90%. As desirable species decline, secondary species become more valuable and subject to exploitation. An issue with this exploitation is that management decisions of fish stocks are often based on political or commercial concerns rather than sound science focussed on preserving stocks, and ultimately, fishing industries. To investigate phylogenetic and phylogeographic relationships of fish, kahawai (Arripis trutta) was used as a proxy species. A. trutta is one of only four members of the genus Arripis, which in turn is the sole member of the family Arripidae. It was found that a single, highly connected population of A. trutta inhabit New Zealand waters, and approximately 15 migrants per generation make the journey between New Zealand and Australia, genetically linking these populations. A phylogeny of A. trutta was resolved using mitochondrial DNA, and while COX1 data supported the hypothesis that A. trutta forms a monophyletic clade within the Stromateoids (medusa fish, squaretails and drift fish) and the Scombrids (tuna, mackerel and their allies) suggesting a common ancestor, other data collected during the investigation does not support this hypothesis.</p>

An Atypical Presentation of Mevalonate Kinase Deficiency in Response to Colchicine Treatment

Mevalonate kinase deficiency (MKD) is a periodic fever syndrome. Nonsteroidal anti-inflammatory drugs, corticosteroids, and anakinra are the most common treatments. However, colchicine is considered insufficient in disease control. In this case report, we present an 8-month-old infant with an atypical presentation of MKD. She had recurrent fever episodes, diarrhea, and lethargy. Elevated mevalonic acid was not detected in the urine. However, the genetic investigation showed a novel pathogenic heterozygous c.925G&#x3e;C (p.Gly309Arg) variant and a heterozygous c.1129G&#x3e;A (p.Val377Ile) mutation in the <i>MVK</i> gene. The patient was treated with colchicine for 8 months. During treatment, no further fever episode had been observed. It should be kept in mind that mevalonic acid excretion may not be present in the urine with mild MKD. Colchicine may be a reasonable option in mild MKD patients for a longer duration of treatment due to favorable adverse event profiles.

Comparative genomics of Bordetella pertussis isolates from New Zealand, a country with an uncommonly high incidence of whooping cough

Whooping cough, the respiratory disease caused by Bordetella pertussis, has undergone a wide-spread resurgence over the last several decades. Previously, we developed a pipeline to assemble the repetitive B. pertussis genome into closed sequences using hybrid nanopore and Illumina sequencing. Here, this sequencing pipeline was used to conduct a more high-throughput, longitudinal screen of 66 strains isolated between 1982 and 2018 in New Zealand. New Zealand has a higher incidence of whooping cough than many other countries; usually at least twice as many cases per 100,000 people as the USA and UK and often even higher, despite similar rates of vaccine uptake. To the best of our knowledge, these strains are the first New Zealand B. pertussis isolates to be sequenced. The analyses here show that, on the whole, genomic trends in New Zealand B. pertussis isolates, such as changing allelic profile in vaccine-related genes and increasing pertactin deficiency, have paralleled those seen elsewhere in the world. At the same time, phylogenetic comparisons of the New Zealand isolates with global isolates suggest that a number of strains are circulating in New Zealand which cluster separately from other global strains, but which are closely related to each other. The results of this study add to a growing body of knowledge regarding recent changes to the B. pertussis genome, and are the first genetic investigation into B. pertussis isolates from New Zealand.