Barber-Say/Ablepharon-Macrostomia : Patient’s View

Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the TWIST2 gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with. We tabulated frequently asked questions from affected individuals and families, and a parent of an affected child and an affected adult woman offered personal testimonies. We focused on perception of illness, body satisfaction, and the consequences for an otherwise normal individual who has a disorder that interferes with body image. The importance of paying particular attention to the management of both the physical appearance and the consequences of these entities on the quality of life is stressed by the affected individuals themselves

Molecular analysis of nondisjunction in mice heterozygous for a Robertsonian translocation.

A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: 1. The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%. 2. Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters. 3. There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction. 4. Strain background did not play an appreciable role in nondisjunction frequency. 5. The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males. 6. The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males. These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals

ANNA CHRISTY Soprano SENIOR RECITAL Friday, February 27, 1998 8:00 p.m. Lillian H. Duncan Recital Hall

Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the TWIST2 gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with. We tabulated frequently asked questions from affected individuals and families, and a parent of an affected child and an affected adult woman offered personal testimonies. We focused on perception of illness, body satisfaction, and the consequences for an otherwise normal individual who has a disorder that interferes with body image. The importance of paying particular attention to the management of both the physical appearance and the consequences of these entities on the quality of life is stressed by the affected individuals themselve

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes

Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations. We identified a recurrent de novo mutation in TWIST2 in seven independent AMS-affected families, as well as another recurrent de novo mutation affecting the same amino acid in ten independent BSS-affected families. Moreover, a genotype-phenotype correlation was observed, because the two syndromes differed based solely upon the nature of the substituting amino acid: a lysine at TWIST2 residue 75 resulted in AMS, whereas a glutamine or alanine yielded BSS. TWIST2 encodes a basic helix-loop-helix transcription factor that regulates the development of mesenchymal tissues. All identified mutations fell in the basic domain of TWIST2 and altered the DNA-binding pattern of Flag-TWIST2 in HeLa cells. Comparison of wild-type and mutant TWIST2 expressed in zebrafish identified abnormal developmental phenotypes and widespread transcriptome changes. Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor's DNA binding

Discovery of a Radiation Component from the Vela Pulsar Reaching 20 Teraelectronvolts

Gamma-ray observations have established energetic isolated pulsars as outstanding particle accelerators and antimatter factories in the Galaxy. There is, however, no consensus regarding the acceleration mechanisms and the radiative processes at play, nor the locations where these take place. The spectra of all observed gamma-ray pulsars to date show strong cutoffs or a break above energies of a few gigaelectronvolt (GeV). Using the H.E.S.S. array of Cherenkov telescopes, we discovered a novel radiation component emerging beyond this generic GeV cutoff in the Vela pulsar's broadband spectrum. The extension of gamma-ray pulsation energies up to at least 20 teraelectronvolts (TeV) shows that Vela pulsar can accelerate particles to Lorentz factors higher than $4\times10^7$. This is an order of magnitude larger than in the case of the Crab pulsar, the only other pulsar detected in the TeV energy range. Our results challenge the state-of-the-art models for high-energy emission of pulsars while providing a new probe, i.e. the energetic multi-TeV component, for constraining the acceleration and emission processes in their extreme energy limit

Discovery of a Radiation Component from the Vela Pulsar Reaching 20 Teraelectronvolts

International audienceGamma-ray observations have established energetic isolated pulsars as outstanding particle accelerators and antimatter factories in the Galaxy. There is, however, no consensus regarding the acceleration mechanisms and the radiative processes at play, nor the locations where these take place. The spectra of all observed gamma-ray pulsars to date show strong cutoffs or a break above energies of a few gigaelectronvolt (GeV). Using the H.E.S.S. array of Cherenkov telescopes, we discovered a novel radiation component emerging beyond this generic GeV cutoff in the Vela pulsar's broadband spectrum. The extension of gamma-ray pulsation energies up to at least 20 teraelectronvolts (TeV) shows that Vela pulsar can accelerate particles to Lorentz factors higher than $4\times10^7$. This is an order of magnitude larger than in the case of the Crab pulsar, the only other pulsar detected in the TeV energy range. Our results challenge the state-of-the-art models for high-energy emission of pulsars while providing a new probe, i.e. the energetic multi-TeV component, for constraining the acceleration and emission processes in their extreme energy limit