Deaf-mute people in history
The Ottoman Sultans used people referred to as "congenital deaf-mutes" (called in Turkish dilsiz or bizeban, i.e. "mute" or "without tongue") in their own personal service from the 15th century to the end of the Ottoman Empire. Due to their nature, they were often entrusted with confidential and delicate missions, including executions. Deaf-muteness in art and literature
Stephen Kings novel The Stand features a main character named Nick Andros who is referred to as "deaf-mute." Though deaf people almost always have a voice, King interpreted the term literally and made Nick unable to vocalize. However, he could read lips and make himself clearly understood by pantomiming and in writing. The phrase is used in The Catcher in the Rye to indicate someone who does not speak his mind, and hears nothing, in effect becoming isolated from the world. Chief Bromden, in One Flew Over the Cuckoos Nest, is believed by all to be deaf and mute, but in fact he can hear and speak; he does not let anyone know this because, as he grew up, he was not spoken to (making him "deaf") and ignored (making him "mute"). The character Singer in the novel The Heart Is a Lonely Hunter, written in 1940, is referred to as "deaf-mute" throughout. In the classic Zorro stories, television series, etc. Zorros aid Bernardo, a mute, pretends that he can also not hear, in order to get information to aid his master in his fight for justice.
Estimates show approximately 10% of children with hypoplastic kidneys are linked to the disease. Many different histological abnormalities have been noted, including:
decrease in nephron number associated with hypertrophy
focal segmental glomerulosclerosis
interstitial fibrosis and tubular atrophy
multicystic dysplastic kidneyUp to one-third of diagnosed patients develop end stage kidney disease, which may lead to complete kidney failure. Causes
Pax2 mutations
The majority of mutations occur in exons 2,3 and 4, which encode the paired domain and frame shift mutations that lead to a null allele. The missense mutations appear to disrupt hydrogen bonds, leading to decreased transactivation of Pax2, but do not seem to effect nuclear localization, steady state mRNA levels, or the ability of Pax2 to bind to its DNA consensus sequence. Mutations related to the disease have also been noted in exons 7,8, and 9, with milder phenotypes than the other mutations. Recent studies
Pax2 is expressed in the kidney, midbrain, hindbrain, cells in the spinal column, developing ear and developing eye. Homozygous negative Pax2 mutation is lethal, but heterozygote mutants showed many symptoms of papillorenal syndrome, including optic nerve dysplasia with abnormal vessels emerging from the periphery of the optic cup and small dysplasic kidneys. It is shown that Pax2 is under upstream control of Shh in both mice and zebrafish, which is expressed in the precordal plate. Other genes
Approximately half of patients with papillorenal syndrome do not have defects in the Pax2. This suggests that other genes play a role in the development of the syndrome, though few downstream effectors of Pax2 have been identified.