Exploring genetic counselors' practice of discussing clinical trials with patients.

Despite concerted and accelerated efforts to increase the knowledge of medicine and disease via clinical studies, clinical trials continue to face low enrollment for all patient groups. The dissemination of the availability of clinical trials to individuals with or at risk for hereditary disorders is critical. This study acts as a foundation in determining an unexplored role of clinical trial discussion in genetic counseling practice.

De novo FRMD5 Missense Variants in Patients with Childhood-Onset Ataxia, Prominent Nystagmus, and Seizures.

Background: FRMD5 variants were recently identified in patients with developmental delay, ataxia, and eye movement abnormalities.

Objectives: We describe 2 patients presenting with childhood-onset ataxia, nystagmus, and seizures carrying pathogenic de novo FRMD5 variants. Weighted gene co-expression network analysis (WGCNA) was performed to gain insights into the function of FRMD5 in the brain.

Novel THAP1 missense variant with incomplete penetrance in a case of generalized young onset dystonia showing good response to deep brain stimulation.

We describe a case of young onset generalized dystonia, harboring a previously unreported likely pathogenic THAP1 missense variant (c.109 G > A; p.Glu37Lys) that was inherited from her unaffected father.

Novel bi-allelic FBXO7 variants in a family with early-onset typical Parkinson's disease.

Bi-allelic mutations in FBXO7 are classically associated with a complex phenotype, known as parkinsonian-pyramidal syndrome. We describe two brothers affected by typical early onset Parkinson's disease (EOPD), who carry novel compound heterozygous variants in FBXO7. Our report highlights that typical EOPD can be part of an expanding FBXO7-related phenotype.

Expanding the spectrum of KCNJ6-related disorders: Milder phenotype with pathological startle responses.

Keppen-Lubinsky syndrome is caused by pathogenic variants in KCNJ6, which encodes the inwardly rectifying channel subfamily J6. The four confirmed cases reported to date were characterized by severe intellectual disability, global developmental delay, feeding difficulties, and dysmorphic features. All but one of the cases also had a severe form of lipodystrophy, resulting in tightly adherent facial skin and appearance of premature aging.

mTORC1 functional assay reveals SZT2 loss-of-function variants and a founder in-frame deletion.

Biallelic pathogenic variants in SZT2 result in a neurodevelopmental disorder with shared features, including early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. SZT2 is as a critical scaffolding protein in the amino acid sensing arm of the mTORC1 signalling pathway. Due to its large size (3432 amino acids), lack of crystal structure, and absence of functional domains, it is difficult to determine the pathogenicity of SZT2 missense and in-frame deletions, but these variants are increasingly detected and reported by clinical genetic testing in individuals with epilepsy.

Dating the skull from Broken Hill, Zambia, and its position in human evolution.

The cranium from Broken Hill (Kabwe) was recovered from cave deposits in 1921, during metal ore mining in what is now Zambia. It is one of the best-preserved skulls of a fossil hominin, and was initially designated as the type specimen of Homo rhodesiensis, but recently it has often been included in the taxon Homo heidelbergensis. However, the original site has since been completely quarried away, and-although the cranium is often estimated to be around 500 thousand years old-its unsystematic recovery impedes its accurate dating and placement in human evolution.

CACNA1H variants are not a cause of monogenic epilepsy.

CACNA1H genetic variants were originally reported in a childhood absence epilepsy cohort. Subsequently, genetic testing for CACNA1H became available and is currently offered by commercial laboratories. However, the current status of CACNA1H as a monogenic cause of epilepsy is controversial, highlighted by ClinGen's recent reclassification of CACNA1H as disputed.

Age estimates for hominin fossils and the onset of the Upper Palaeolithic at Denisova Cave.

Denisova Cave in the Siberian Altai (Russia) is a key site for understanding the complex relationships between hominin groups that inhabited Eurasia in the Middle and Late Pleistocene epoch. DNA sequenced from human remains found at this site has revealed the presence of a hitherto unknown hominin group, the Denisovans, and high-coverage genomes from both Neanderthal and Denisovan fossils provide evidence for admixture between these two populations. Determining the age of these fossils is important if we are to understand the nature of hominin interaction, and aspects of their cultural and subsistence adaptations.

Homo sapiens in Arabia by 85,000 years ago.

Understanding the timing and character of the expansion of Homo sapiens out of Africa is critical for inferring the colonization and admixture processes that underpin global population history. It has been argued that dispersal out of Africa had an early phase, particularly ~130-90 thousand years ago (ka), that reached only the East Mediterranean Levant, and a later phase, ~60-50 ka, that extended across the diverse environments of Eurasia to Sahul. However, recent findings from East Asia and Sahul challenge this model.

The earliest modern humans outside Africa.

To date, the earliest modern human fossils found outside of Africa are dated to around 90,000 to 120,000 years ago at the Levantine sites of Skhul and Qafzeh. A maxilla and associated dentition recently discovered at Misliya Cave, Israel, was dated to 177,000 to 194,000 years ago, suggesting that members of the clade left Africa earlier than previously thought. This finding changes our view on modern human dispersal and is consistent with recent genetic studies, which have posited the possibility of an earlier dispersal of around 220,000 years ago.

The Impact of Family History on the Clinical Features of Huntington's Disease.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. In most cases the disease is inherited from a parent, although a considerable number of affected persons have no reported family history of the disease. While CAG repeat length is negatively correlated with age of symptom onset, variability exists suggesting that other variables may influence symptom onset.

An early modern human presence in Sumatra 73,000-63,000 years ago.

Genetic evidence for anatomically modern humans (AMH) out of Africa before 75 thousand years ago (ka) and in island southeast Asia (ISEA) before 60 ka (93-61 ka) predates accepted archaeological records of occupation in the region. Claims that AMH arrived in ISEA before 60 ka (ref. 4) have been supported only by equivocal or non-skeletal evidence.

Direct U-series analysis of the Lezetxiki humerus reveals a Middle Pleistocene age for human remains in the Basque Country (northern Iberia).

In 1964, a human humerus was found in a sedimentary deposit in Lezetxiki Cave (Basque Country, northern Iberia). The first studies on the stratigraphy, associated mammal faunal remains and lithic implements placed the deposits containing the humerus into the Riss glacial stage. Direct chronometric evidence has so far been missing, and the previous chronostratigraphic framework and faunal dating gave inconsistent results.

The first archaic Homo from Taiwan.

Recent studies of an increasing number of hominin fossils highlight regional and chronological diversities of archaic Homo in the Pleistocene of eastern Asia. However, such a realization is still based on limited geographical occurrences mainly from Indonesia, China and Russian Altai. Here we describe a newly discovered archaic Homo mandible from Taiwan (Penghu 1), which further increases the diversity of Pleistocene Asian hominins.

Pleistocene cave art from Sulawesi, Indonesia.

Archaeologists have long been puzzled by the appearance in Europe ∼40-35 thousand years (kyr) ago of a rich corpus of sophisticated artworks, including parietal art (that is, paintings, drawings and engravings on immobile rock surfaces) and portable art (for example, carved figurines), and the absence or scarcity of equivalent, well-dated evidence elsewhere, especially along early human migration routes in South Asia and the Far East, including Wallacea and Australia, where modern humans (Homo sapiens) were established by 50 kyr ago. Here, using uranium-series dating of coralloid speleothems directly associated with 12 human hand stencils and two figurative animal depictions from seven cave sites in the Maros karsts of Sulawesi, we show that rock art traditions on this Indonesian island are at least compatible in age with the oldest European art. The earliest dated image from Maros, with a minimum age of 39.

Middle pleistocene human remains from Tourville-la-Rivière (Normandy, France) and their archaeological context.

Despite numerous sites of great antiquity having been excavated since the end of the 19th century, Middle Pleistocene human fossils are still extremely rare in northwestern Europe. Apart from the two partial crania from Biache-Saint-Vaast in northern France, all known human fossils from this period have been found from ten sites in either Germany or England. Here we report the discovery of three long bones from the same left upper limb discovered at the open-air site of Tourville-la-Rivière in the Seine Valley of northern France.

Reproductive decision-making among individuals at risk for familial amyotrophic lateral sclerosis.

This qualitative study explored the reproductive decision-making process in individuals at 50% risk for familial amyotrophic lateral sclerosis (FALS) from families with a known genetic mutation. We spoke with 10 individuals utilizing a semi-structured interview. Participants had a first-degree relative with FALS, made reproductive decisions in the past 30 years and did not know their genetic status during decision-making.

An evaluation of the use of reptile dermal scutes as a non-invasive method to monitor mercury concentrations in the environment.

Reptiles are ideal organisms for the non-invasive monitoring of mercury (Hg) contamination. We have investigated Hg bioaccumulation in tissue layers of reptile dermis as a basis for establishing a standardized collection method for Hg analysis. Tissue samples from freshwater turtle species Podocnemis unifilis and Podocnemis expansa and caiman species Melanosuchus niger and Caiman crocodilus, all from the Amazonian region, were analysed in this study.

The chronostratigraphy of the Haua Fteah cave (Cyrenaica, northeast Libya).

The 1950s excavations by Charles McBurney in the Haua Fteah, a large karstic cave on the coast of northeast Libya, revealed a deep sequence of human occupation. Most subsequent research on North African prehistory refers to his discoveries and interpretations, but the chronology of its archaeological and geological sequences has been based on very early age determinations. This paper reports on the initial results of a comprehensive multi-method dating program undertaken as part of new work at the site, involving radiocarbon dating of charcoal, land snails and marine shell, cryptotephra investigations, optically stimulated luminescence (OSL) dating of sediments, and electron spin resonance (ESR) dating of tooth enamel.

U-series and radiocarbon analyses of human and faunal remains from Wajak, Indonesia.

Laser ablation U-series dating results on human and faunal bone fragments from Wajak, Indonesia, indicate a minimum age of between 37.4 and 28.5 ka (thousands of years ago) for the whole assemblage.

Confirmation of a late middle Pleistocene age for the Omo Kibish 1 cranium by direct uranium-series dating.

While it is generally accepted that modern humans evolved in Africa, the specific physical evidence for that origin remains disputed. The modern-looking Omo 1 skeleton, discovered in the Kibish region of Ethiopia in 1967, was controversially dated at ~130 ka (thousands of years ago) by U-series dating on associated Mollusca, and it was not until 2005 that Ar-Ar dating on associated feldspar crystals in pumice clasts provided evidence for an even older age of ~195 ka. However, questions continue to be raised about the age and stratigraphic position of this crucial fossil specimen.

Small amounts of zinc from zinc oxide particles in sunscreens applied outdoors are absorbed through human skin.

Metal oxide nanoparticles are commonly used in personal-care formulations as protective agents against exposure to ultraviolet radiation. Although previous research has concluded that nanoparticles do not penetrate healthy skin, it remains contentious whether this conclusion holds under normal conditions of sunscreen use. Humans (n = 20) were exposed to sunscreens containing zinc oxide (ZnO) particles to determine if Zn from the particles was absorbed through skin over five consecutive days under outdoor conditions.