Post-Zygotic Rescue of Meiotic Errors Causes Brain Mosaicism and Focal Epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development

Post-zygotic Rescue of Meiotic Errors Causes Brain Mosaicism and Focal Epilepsy

Somatic mosaicism is a known cause of neurological disorders, including developmental brain malformations and epilepsy. Brain mosaicism is traditionally attributed to post-zygotic genetic alterations arising in fetal development. Here we describe post-zygotic rescue of meiotic errors as an alternate origin of brain mosaicism in patients with focal epilepsy who have mosaic chromosome 1q copy number gains. Genomic analysis showed evidence of an extra parentally derived chromosome 1q allele in the resected brain tissue from five of six patients. This copy number gain is observed only in patient brain tissue, but not in blood or buccal cells, and is strongly enriched in astrocytes. Astrocytes carrying chromosome 1q gains exhibit distinct gene expression signatures and hyaline inclusions, supporting a novel genetic association for astrocytic inclusions in epilepsy. Further, these data demonstrate an alternate mechanism of brain chromosomal mosaicism, with parentally derived copy number gain isolated to brain, reflecting rescue in other tissues during development

Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria mitochondrial disorder: case report and literature review

Background: Leigh syndrome is a rare, genetic, and severe mitochondrial disorder characterized by neuromuscular issues (ataxia, seizure, hypotonia, developmental delay, dystonia) and ocular abnormalities (nystagmus, atrophy, strabismus, ptosis). It is caused by pathogenic variants in either mitochondrial or nuclear DNA genes, with an estimated incidence rate of 1 per 40,000 live births.Case presentation: Herein, we present an infant male with nystagmus, hypotonia, and developmental delay who carried a clinical diagnosis of Leigh-like syndrome. Cerebral magnetic resonance imaging changes further supported the clinical evidence of an underlying mitochondrial disorder, but extensive diagnostic testing was negative. Trio exome sequencing under a research protocol uncovered compound-heterozygous missense variants in the HTRA2 gene (MIM: #606441): NM_013247.5:c.1037A>T:(p.Glu346Val) (maternal) and NM_013247.5:c.1172T>A:(p.Val391Glu) (paternal). Both variants are absent from public databases, making them extremely rare in the population. The maternal variant is adjacent to an exon-intron boundary and predicted to disrupt splicing, while the paternal variant alters a highly conserved amino acid and is predicted to be damaging by nearly all in silico tools. Biallelic variants in HTRA2 cause 3-methylglutaconic aciduria, type VIII (MGCA8), an extremely rare autosomal recessive disorder with fewer than ten families reported to date. Variant interpretation is challenging given the paucity of known disease-causing variants, and indeed we assess both paternal and maternal variants as Variants of Uncertain Significance under current American College of Medical Genetics guidelines. However, based on the inheritance pattern, suggestive evidence of pathogenicity, and significant clinical correlation with other reported MGCA8 patients, the clinical care team considers this a diagnostic result.Conclusion: Our findings ended the diagnostic odyssey for this family and provide further insights into the genetic and clinical spectrum of this critically under-studied disorder

Data from: The velvet spiders: an atlas of the Eresidae (Arachnida, Araneae)

The family Eresidae C. L. Koch, 1850 is reviewed at the genus level. The family comprises nine genera including one new genus. They are: Adonea Simon, 1873, Dorceus C. L. Koch, 1846, Dresserus Simon, 1876, Eresus Walckenaer, 1805, Gandanameno Lehtinen, 1967, Loureedia gen. n., Paradonea Lawrence, 1968, Seothyra Purcell, 1903, and Stegodyphus Simon, 1873. A key to all genera and major lineages is provided along with corresponding diagnoses, as well as descriptions of selected species. These are documented with collections of photographs, scanning electron micrographs, and illustrations. A new phylogeny of Eresidae based on molecular sequence data expands on a previously published analysis. A species of the genus Paradonea Lawrence, 1968 is sequenced and placed phylogenetically for the first time. New sequences from twenty Gandanameno Lehtinen, 1967 specimens were added to investigate species limits within the genus. The genus Loureedia gen. n. is proposed to accommodate Eresus annulipes Lucas, 1857. Two species, Eresus semicanus Simon, 1908 and Eresus jerbae El-Hennawy, 2005, are synonymized with Loureedia annulipes comb. n. One new species, Paradonea presleyi sp. n. is described. Eresus algericus El-Hennawy, 2004 is transferred to Adonea Simon, 1873. The female of Dorceus fastuosus C. L. Koch, 1846 is described for the first time. The first figures depicting Paradonea splendens (Lawrence, 1936) are presented

Biomaterial Evolution Parallels Behavioral Innovation in the Origin of Orb-lIke Spider Webs

Correlated evolution of traits can act synergistically to facilitate organism function. But, what happens when constraints exist on the evolvability of some traits, but not others? The orb web was a key innovation in the origin of \u3e12,000 species of spiders. Orb evolution hinged upon the origin of novel spinning behaviors and innovations in silk material properties. In particular, a new major ampullate spidroin protein (MaSp2) increased silk extensibility and toughness, playing a critical role in how orb webs stop flying insects. Here, we show convergence between pseudo-orb-weaving Fecenia and true orb spiders. As in the origin of true orbs, Fecenia dragline silk improved significantly compared to relatives. But, Fecenia silk lacks the high compliance and extensibility found in true orb spiders, likely due in part to the absence of MaSp2. Our results suggest how constraints limit convergent evolution and provide insight into the evolution of nature\u27s toughest fibers

The velvet spiders: an atlas of the Eresidae (Arachnida, Araneae)

The family Eresidae C. L. Koch, 1850 is reviewed at the genus level. The family comprises nine genera including one new genus. They are: Adonea Simon, 1873, Dorceus C. L. Koch, 1846, Dresserus Simon, 1876, Eresus Walckenaer, 1805, Gandanameno Lehtinen, 1967, Loureedia gen. n., Paradonea Lawrence, 1968, Seothyra Purcell, 1903, and Stegodyphus Simon, 1873. A key to all genera and major lineages is provided along with corresponding diagnoses, as well as descriptions of selected species. These are documented with collections of photographs, scanning electron micrographs, and illustrations. A new phylogeny of Eresidae based on molecular sequence data expands on a previously published analysis. A species of the genus Paradonea Lawrence, 1968 is sequenced and placed phylogenetically for the first time. New sequences from twenty Gandanameno Lehtinen, 1967 specimens were added to investigate species limits within the genus. The genus Loureedia gen. n. is proposed to accommodate Eresus annulipes Lucas, 1857. Two species, Eresus semicanus Simon, 1908 and Eresus jerbae El-Hennawy, 2005, are synonymized with Loureedia annulipes comb. n. One new species, Paradonea presleyi sp. n. is described. Eresus algericus El-Hennawy, 2004 is transferred to Adonea Simon, 1873. The female of Dorceus fastuosus C. L. Koch, 1846 is described for the first time. The first figures depicting Paradonea splendens (Lawrence, 1936) are presented

Milleretal_Eresidae

KML (Keyhole Markup Language) file for viewing specimen occurence records interactively in Google Earth (http://earth.google.com/)

Milleretal_EresidaeSupplementaryDocs

Electronic supplementary documents. Figure S1.: Bayesian phylogenetic tree. Figure S2: Photographs of copulatory organs from Gandanameno specimens used in molecular phylogenetic analysis. Figure S3: Photographs of copulatory organs from Gandanameno specimens used in molecular phylogenetic analysis

Milleretal_ZookeysMatrix

Phylogenetic data matrix based on aligned molecular sequence data including commands for running analysis in Mr Bayes