Autosomal Dominant Non-Syndromic Hearing Loss Maps to DFNA33 (13q34) and Co-Segregates with Splice Site Variants in ATP11A, A Phospholipid Flippase Gene

Whole genome approaches are superior for identifying recessive genes, however discovery of dominant genes including deafness genes (DFNA) remains challenging. Herein we report a new DFNA gene, ATP11A, in a Newfoundland family with a variable form of bilateral sensorineural hearing loss (SNHL). Targeted screening of DFNA genes based on audioprofiles was unsuccessful. Genome-wide SNP genotyping linked SNHL to DFNA33 (Lod = 4.77), a locus on 13q34 previously mapped in a German family with variable SNHL in 2009. WGS identified 51 unremarkable positional variants on 13q34. Continuous clinical ascertainment identified several key recombination events and reduced the disease interval to 769 Kb, excluding all but one variant. ATP11A (NC_000013.11: g.190616G > A) is a novel point mutation predicted to be a cryptic donor splice site. RNA studies in patient-derived tissues verified in silico predictions, revealing the retention of 153bp of intron in the 3’ UTR of several ATP11A isoforms. A second, unresolved family from Israel with a similar, variable form of SNHL and a novel duplication in exon 28 of ATP11A that occurs within the splice donor sequence (intron 28). ATP11A is a type of P4-ATPase that transports (flip) phospholipids from the outer to inner leaflet of cell membranes to maintain asymmetry. Haploinsufficiency of ATP11A, the phospholipid flippase that specially transports phosphatidylserine (PS) and phosphatidylethanolamine (PE), could leave cells with PS/PE at the extracellular side vulnerable to phagocytic degradation. Given that surface PS can be pharmaceutically targeted, hearing loss due to ATP11A could potentially be treated. It is also likely that ATP11A is the gene underlying DFNA33.

Identification of Cryptotermes brevis (Walker, 1853) and Kalotermes flavicollis (Fabricius, 1793) Termite Species by Detritus Analysis

We carried out morphological and dimensional analysis of the detritic elements deposited in the galleries of two termite species of the Kalotermitidae family present in Spain known as drywood termites (Cryptotermes brevis (Walker, 1853) and Kalotermes flavicollis (Fabricius, 1793)). This was in order to gauge the possibility of differentiating the species only on the basis of debris observation and analysis. Ten samples from six different geographical sources were analyzed and measured. Significant statistical differences were found between these two termite species in all measured parameters, and multivariate statistical models, able to predict species on the basis of dimensional measurements, were developed, with a degree of success higher than 75%. The most important dimensional differences were length and width, as well as the variable hexagonal shape of the cross-section of the detritic elements. The detritic elements of both species had a variable form of a hexagonal prism with slightly concave faces, and with pointed or rounded ends. Those of the Cryptotermes brevis species were significantly larger, less elongated, and had a smaller concavity on the faces of the prism. Color was found to be particularly variable in both species, and was not useful. Nevertheless, the debris of Kalotermes flavicollis was markedly “dirty” (mixed with other wood remains).

The kṛṣṇāṣṭamīvrata in the Śivadharmaśāstra

This article investigates the textual basis of the kṛṣṇāṣṭamīvrata, an observance first attested in the tenth chapter of the Śivadharmaśāstra. Given the great variety in readings of the versions contained in manuscripts that are of distinctly variegated geographical provenance and age, it is argued that at least during the 6th to 7th centuries—and even possibly later—the kṛṣṇāṣṭamīvrata had not yet developed a consistent form. The variable form of this particular vrata stands in stark contrast to its Vaiṣṇavite precursors that at the time of composition of the Śivadharmaśāstra had already developed into a standardized, canonical form. Hence, we argue, the regional variation of the manuscripts is indicative of a living, widespread Śaivite tradition that gives rise to different lines of transmission. Since the chief aim of this contribution is to display and study this variation, the kernel of this article consists of a ‘comparative edition’ of the tenth chapter of Śivadharmaśāstra, furnished with translation and philological commentary.