An Initiation Rite in Tibetan Historiography

I shall investigate a quasi-historical event in the biographies of the second ‘Dharma King’ of the Tibetan Empire, Khri-srong Lde-btsan (Trisong Detsen). As the newborn heir to the throne, he was stolen from his mother by a rival queen; however, at a ceremonial event the still infant prince indicated his true descent by sitting on the lap of his maternal uncle. As Ruzsa (2016) noticed, the complex motif of the new ruler choosing his family by sitting on the lap of a male representative can be found in the Indian legend of Śunaḥśepa, embedded in a much richer structure. Following his reconstruction, by analysing further parallelisms in a wider corpus, it appears that the seemingly innocent story of a baby prince is, in fact, a remnant of an archaic rite. I suppose that originally this was a rite of passage, a special variant of puberty initiation: the consecration of the heir apparent. Furthermore, its relationship to the Indian legend of Śunaḥśepa connects it indirectly with the stories of Isaac and even Snow White and also with several rites of passage in ancient Greece. I will also suggest that some versions of the legend point to a probably even more archaic cycle of maternity rites with parallels in Solomon’s judgment and the Chinese Chalk Circle.

SYN1 Mutation Causes X-Linked Toothbrushing Epilepsy in a Chinese Family

Toothbrushing epilepsy is a rare form of reflex epilepsy (RE) with sporadic incidence. To characterize the genetic profile of reflex epilepsy patients with tooth brushing-induced seizures in a Chinese family. Solo clinical whole-exome sequencing (WES) of the proband, a 37-year-old Chinese man, was performed to characterize the genetic etiology of toothbrushing epilepsy. Mutations in the maternal X-linked synapsin 1 (SYN1) identified in the proband and his family members were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined using in silico analysis. The proband had four episodes of toothbrushing-induced seizures. The semiology included nausea, twitching of the right side of the mouth and face, followed by a generalized tonic-clonic seizure (GTCS). The proband's elder maternal uncle had three toothbrushing-induced epileptic seizures at the age of 26. The proband's younger maternal uncle had no history of epileptic seizures but had a learning disability and aggressive tendencies. We identified a deleterious nonsense mutation, c.1807C>T (p.Q603Ter), in exon 12 of the SYN1 gene (NM_006950), which can result in a truncated SYN1 phosphoprotein with altered flexibility and hydropathicity. This novel mutation has not been reported in the 1000G, EVS, ExAC, gnomAD, or HGMD databases. We identified a novel X-linked SYN1 exon 12 mutant gene in a Chinese family with toothbrushing epilepsy. Our findings provide novel insights into the mechanism of this complex form of reflex epilepsy that could potentially be applied in disease diagnosis.

A rare thyroid disorder mimicking mitochondrial disease

Introduction. Patients affected with Allan-Herndon-Dudley syndrome (AHDS) have a deficiency of monocarboxylate transporter 8 (MCT8), a protein primarily responsible for the transport of triiodothyronine (T3) into the brain. This X-linked disorder affects almost exclusively males with clinical presentation encompassing developmental delay, axial hypotonia, dystonia, poor head control, quadriplegia and absence of speech. Case reports. Patient 1 is a male child referred to a hospital investigation at 11 months due to severe developmental delay and elevated blood ammonia level (163 mcmol/L). Hypotonia and dystonic movements were noted at admission, with facial dysmorphic features. Laboratory findings revealed increased blood lactate (17.2 mmol/L), alanine (533 mcmol/L) and ammonia (391 mcmol/L) concentrations. Serum creatine-kinase levels showed substantial increase over the course of hospitalization up to 6,855 IU/L. Clinical exome sequencing detected a novel hemizygous frameshift insertion c.1456insC in gene SLC16A2, predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Segregation genetic testing of the family members revealed that mother, maternal uncle and maternal grandmother carry the same mutation in SLC16A2. The boy`s mother experienced learning difficulties through childhood while maternal uncle is severely affected by AHDS. Patient 2 is a boy referred to clinical geneticist due to severe psychomotor delay of unknown etiology. Moderate serum lactate elevation was the only laboratory abnormality during initial investigations. Diagnosis of AHDS was established by clinical exome sequencing, and subsequent hormonal evaluation revealed increased triiodothyronine (T3) level which corresponds well to genetic diagnosis. Conclusion. Presence of lactic acidosis and/or hyperammonemia in children with severe developmental delay is not specific for inborn disorders of energy production, such as mitochondrial disease. Clinicians should consider thyroid hormones profiling in cases of unexplained severe developmental delay in male children, especially if associated with axial hypotonia and dystonic movements.

Cerebellar ataxia, neuropathy, hearing loss, and intellectual disability due to AIFM1 mutation

ObjectiveTo describe the clinical and molecular genetic findings in a family segregating a novel mutation in the AIFM1 gene on the X chromosome.MethodsWe studied the clinical features and performed brain MRI scans, nerve conduction studies, audiometry, cognitive testing, and clinical exome sequencing (CES) in the proband, his mother, and maternal uncle. We used in silico tools, X chromosome inactivation assessment, and Western blot analysis to predict the consequences of an AIFM1 variant identified by CES and demonstrate its pathogenicity.ResultsThe proband and his maternal uncle presented with childhood-onset nonprogressive cerebellar ataxia, hearing loss, intellectual disability (ID), peripheral neuropathy, and mood and behavioral disorder. The proband's mother had mild cerebellar ataxia, ID, and mood and behavior disorder, but no neuropathy or hearing loss. The 3 subjects shared a variant (c.1195G>A; p.Gly399Ser) in exon 12 of the AIFM1 gene, which is not reported in the exome/genome sequence databases, affecting a critical amino acid for protein function involved in NAD(H) binding and predicted to be pathogenic with very high probability by variant analysis programs. X chromosome inactivation was highly skewed in the proband's mother. The mutation did not cause quantitative changes in protein abundance.ConclusionsOur report extends the molecular and phenotypic spectrum of AIFM1 mutations. Specific findings include limited progression of neurologic abnormalities after the first decade and the coexistence of mood and behavior disorder. This family also shows the confounding effect on the phenotype of nongenetic factors, such as alcohol and drug use and side effects of medication.

A novo missense variant of the PHEX gene in patients with X-linked dominant hypophosphatemia

X-linked hypophosphatemia (XLH) is characterized by low serum phosphate concentration. Both males and females could be affected, and males tend to perform more severely. Identification of a pathological variation in the phosphate-regulating gene with homologies to endopeptidase on the X chromosome ( PHEX ) gene regulating phosphate located in the X chromosome by molecular genetic detection confirms the diagnosis. The current pharmacologic treatments mainly focus on relieving symptoms instead of preventing it occur. A maternally inherited novo missense heterozygous variant c.1256G>A in exon 11 of the PHEX gene was found in the proband and her mother. SIFT, Polyphen2 and PROVEAN predicted it as a deleterious mutation. This mutation was also detected in an affected maternal grandmother and an affected maternal uncle, a healthy maternal uncle and three healthy maternal aunts and their offspring did not carry this mutation. We identified a novo PHEX variant c.1256G>A, p.(Gly419Glu), the heterozygous mutation may be the cause of the deformity in this family.

Red Bird and Sequoyah: A Reply to Simek et al.

Red Bird was a Cherokee murdered at the Red Bird River Petroglyph site (15Cy51) and buried at the Red Bird River Rockshelter (15Cy52) during the late eighteenth century, where he left an important record of traditional petroglyphs. His legacy is key to understanding the origins of Sequoyah's Cherokee Syllabary and its relationship to rock art. Personal testimonies of Red Bird's descendants are supported by primary documents and archaeological evidence, including the letters of Sequoyah's maternal uncle, John Watts, and prototypes of Cherokee Syllabary characters engraved at 15Cy52 in 1808, when members of Sequoyah's matrilineal family resided nearby.

One piece of the matrilineal puzzle: the socioecology of maternal uncle investment

Maternal uncle relationships in which men invest resources (usually in the form of inheritance of material wealth) into their sisters' children are characteristic of matrilineal systems and hypothesized to arise under certain socioecological circumstances, but little research has systematically investigated conditions that are associated with this type of investment. We quantify relationships between household-level socioeconomic variables and different types of maternal uncle investment (direct care and indirect resource investment) within a bilateral, semi-nomadic population. Shodagor people of Bangladesh allow us to consider matrilineal behaviours in an evolutionary framework owing to their flexible social structure in which 39% of families receive some investment from a maternal uncle. Variables associated with direct maternal uncle care reflect the significance of maintaining consistent residence throughout the year and an increased need for childcare in families residing on boats versus those living on the land. Informative predictors of indirect investment indicate that a mother's birth history corresponds with more tangible contributions such as food and clothing. These results identify household-level variables specific to direct versus indirect maternal uncle investment, whereas having more older brothers or being firstborn increased the odds of a mother receiving any investment from brothers at all. Exploring these social and ecological associations in a bilateral, relatively flexible population unveils household circumstances that may lead to the development of female-biased kinship. This article is part of the theme issue ‘The evolution of female-biased kinship in humans and other mammals'.

One Piece of the Matrilineal Puzzle: The Socioecology of Maternal Uncle Investment

Maternal uncle relationships in which men invest resources (usually in the form of inheritance of material wealth) into their sisters’ children are characteristic of matrilineal systems and hypothesized to arise under certain socio-ecological circumstances, but little research has systematically investigated conditions that are associated with this type of investment. We quantify relationships between household-level socio-economic variables and different types of maternal uncle investment (direct care and indirect resource investment) within a bilateral, semi- nomadic population. The Shodagor allow us to consider matrilineal behaviors in an evolutionary framework due to their flexible social structure in which 39% of families receive some investment from a maternal uncle. Variables associated with direct maternal uncle care reflect the significance of maintaining consistent residence throughout the year and an increased need for childcare in families residing on boats versus those living on the land. Informative predictors of indirect investment indicate that a mother’s birth history corresponds with more tangible contributions such as food and clothing. These results identify household-level variables specific to direct versus indirect maternal uncle investment, whereas having more older brothers or being firstborn increased the odds of a mother receiving any brotherly investment at all. Exploring these social and ecological associations in a bilateral, relatively flexible population unveils household circumstances that may lead to the development of female-biased kinship.

Family

Servilia’s patrician paternal line, the Servilii Caepiones, descended from Cn. Servilius Caepio consul 253. Servilia’s great-grandfather was probably Cn. Caepio consul 141, censor 125. His presumed second son won a triumph and the consulship of 106. This man proposed a law on the panels of judges. His defeat by the Cimbri at Arausio in 105 wrecked his career. Driven into exile, he gave up his citizenship. His son, Q. Caepio, possibly by a Metella, married Livia. Her family, the Livii Drusi, had distinguished themselves in the second century. Her father was tribune 122, consul 112, triumphed, and died as censor 109. Livia and Caepio produced a daughter, Servilia (c.100), and a son. They divorced and Livia married Cato, to whom she bore two children. On the deaths of Cato and Livia, the four children lived with their maternal uncle M. Drusus and perhaps his wife and his mother.