Differential DNA methylation of vocal and facial anatomy genes in modern humans.

Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.

Familial Sulcus Vergeture: Further Evidence for Congenital Origin of Type 2 Sulcus.

A 29-year-old otherwise healthy woman presented with a lifetime history of hoarseness because it had begun to interfere with her career. Examination of both the woman and her 60-year-old father revealed bilateral sulcus vergeture, without inflammation or lesions attributable to phonotrauma. The woman responded well to injection augmentation; the father declined treatment. Combined with existing descriptions of other family groupings, all with sulcus vergeture without signs of inflammation, clinical progression, and little or no apparent behavioral component, this report further suggests that sulcus vergeture (Ford type 2) and sulcus vocalis (Ford type 3) are entirely different entities, despite architectural similarity.

Effects of raised-intensity phonation on inflammatory mediator gene expression in normal rabbit vocal fold.

OBJECTIVE: To investigate the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory messenger RNA (mRNA) expression in vivo. STUDY DESIGN: Prospective animal study. SETTING: Laboratory. SUBJECTS AND METHODS: Ten New Zealand White breeder rabbits received 30 minutes of experimentally induced modal or raised-intensity phonation, followed by a 30-minute recovery period. A separate group of five rabbits served as sham controls. Real-time polymerase chain reaction was performed to investigate the mRNA expression of interleukin 1beta (IL-1beta), transforming growth factor beta-1 (TGFbeta1), and cyclooxygenase-2 (COX-2). Separate one-way analysis of variance (ANOVA) tests were used to investigate differences in gene expression across groups, with an appropriate alpha correction of 0.016 to control for type I error. Significant main effects were further examined using Fisher's least significant difference. RESULTS: ANOVA revealed that there were differences for IL-1beta, TGFbeta1, and COX-2 between sham control, modal phonation, and raised-intensity phonation (P 0.0001). Pairwise comparisons revealed that the expression of IL-1beta, COX-2, and TGFbeta1 increased significantly during raised-intensity phonation, compared to modal phonation and sham control (P 0.0001). CONCLUSION: Results provided support for the hypothesis that a transient episode of raised-intensity phonation causes a significant increase in vocal fold inflammatory mRNA expression. Future studies will investigate the signal transduction pathways and mechanisms regulating the vocal fold inflammatory response. The long-term goal of these studies is to advance understanding of the molecular and cellular events underlying phonation-related tissue alterations.

Experimentally induced phonation increases matrix metalloproteinase-1 gene expression in normal rabbit vocal fold.

OBJECTIVES: An in vivo rabbit model was used to study the effect of 3 hours of experimentally induced phonation on messenger RNA expression of the normal vocal fold. STUDY DESIGN: Prospective; animal model. SUBJECTS AND METHODS: Ten rabbits received experimental phonation for 3 hours, followed by 1 hour of recovery. A separate group of 5 rabbits served as no-phonation controls. We measured messenger RNA expression of matrix metalloproteinase-1, MMP-9, and interleukin-1beta using real-time reverse-transcribed polymerase chain reaction. Gene expression ratios from phonation and control animals were assessed with the Mann-Whitney U test. RESULTS: Phonation (77 +/- 3 dB; 429 +/- 141 Hz) resulted in increased matrix metalloproteinase-1 gene expression from rabbits receiving experimental phonation compared with controls, and a nonsignificant increase in matrix metalloproteinase-9 and interleukin-1beta gene expression. CONCLUSION: Matrix metalloproteinases play a role in maintaining tissue homeostasis. Investigation of cellular responses to experimental phonation may provide insight into how matrix metalloproteinases and other extracellular matrices contribute to maintenance of the vocal fold and development of pathology.

Neurological aspects of del(1q) syndrome.

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions.