[Age influence in otoacoustic emissions for hearing loss screening in infants]. / Influencia de la edad en las otoemisiones acústicas para el screening de hipoacusia infantil.

OBJECTIVE: To determine the most favorable age for detection of otoacoustic emissions in newborns and for repeated testing. METHODS: Observational, retrospective, descriptive study in 2,567 newborns. RESULTS: The incidence of any degree of hearing loss was 7 per thousand newborns. It was proportionately higher in the group that did not have otologic risk factors The distribution of otoacoustic emissions by age groups followed a significant linear trend in the first month of life. The time lapse to obtain a positive result on the second otoacoustic emission test was 6 days from the first one. CONCLUSIONS: Otoacoustic emission screening should be performed in all newborns as late as possible after birth (from the first 48 hours after birth), but before hospital discharge for the test to be effective and efficient. A repeat test, if required, must be performed at least six days after failing the first one.

Influencia de la edad en las otoemisiones acústicas para el screening de hipoacusia infantil / Age influence in otoacoustic emissions for hearing loss screening in infants

Objetivo: Determinar cuál es la edad más adecuada en el recién nacido para la detección de Otoemisiones y el tiempo medio necesario para la normalización en las repeticiones, Método: Estudio observacional, retrospectivo y descriptivo sobre 2.567 recién nacidos. Resultados: La prevalencia de hipoacusia de cualquier grado fue del 7 por mil (mayor proporcionalmente en el grupo sin factores de riesgo otológico: 5 frente al 2 por mil con factores positivos). Los resultados por grupos de edad siguieron una tendencia lineal significativa en el primer mes. La segunda Otoemisión se positivizó transcurridos 6 días desde la realización del primer test. Conclusiones: Las Otoemisiones deben hacerse a todos los recién nacidos lo más tardíamente posible antes del alta hospitalaria (a partir de las primeras 48 horas) para que la prueba sea rentable. Si es necesaria la repetición se hará al menos seis días después del fallo en la primera prueba (AU)

OBJECTIVE: To determine the most favorable age for detection of otoacoustic emissions in newborns and for repeated testing. METHODS: Observational, retrospective, descriptive study in 2,567 newborns. RESULTS: The incidence of any degree of hearing loss was 7 per thousand newborns. It was proportionately higher in the group that did not have otologic risk factors The distribution of otoacoustic emissions by age groups followed a significant linear trend in the first month of life. The time lapse to obtain a positive result on the second otoacoustic emission test was 6 days from the first one. CONCLUSIONS: Otoacoustic emission screening should be performed in all newborns as late as possible after birth (from the first 48 hours after birth), but before hospital discharge for the test to be effective and efficient. A repeat test, if required, must be performed at least six days after failing the first one (AU)

Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies.

The Drosophila gene sine oculis (so), a nuclear homeoprotein that is required for eye development, has several homologues in vertebrates (the SIX gene family). Among them, SIX3 is considered to be the functional orthologue of so because it is strongly expressed in the developing eye. However, embryonic SIX3 expression is not limited to the eye field, and SIX3 has been found to be mutated in some patients with holoprosencephaly type 2 (HPE2), suggesting that SIX3 has wide implications in head development. We report here the cloning and characterization of SIX6, a novel human SIX gene that is the homologue of the chick Six6(Optx2) gene. SIX6 is closely related to SIX3 and is expressed in the developing and adult human retina. Data from chick and mouse suggest that the human SIX6 gene is also expressed in the hypothalamic and the pituitary regions. SIX6 spans 2567 bp of genomic DNA and is split in two exons that are transcribed into a 1393-nucleotide-long mRNA. Chromosomal mapping of SIX6 revealed that it is closely linked to SIX1 and SIX4 in human chromosome 14q22.3-q23, which provides clues about the origin and evolution of the vertebrate SIX family. Recently three independent reports have associated interstitial deletions at 14q22.3-q23 with bilateral anophthalmia and pituitary anomalies. Genomic analyses of one of these cases demonstrated SIX6 hemizygosity, strongly suggesting that SIX6 haploinsufficiency is responsible for these developmental disorders.

Six9 (Optx2), a new member of the six gene family of transcription factors, is expressed at early stages of vertebrate ocular and pituitary development.

The Drosophila gene sine oculis (so) is a nuclear homeoprotein, which is required for eye development. Several homologues of so have been found in vertebrates. We report here a detailed expression analysis in chick and mouse of Six9 (Optx2), a novel gene of the Six/sine oculis family closely related to Six3. Six9 (Optx2) is first expressed at presomitic stages in the head-fold, both in the neural plate and in the underlying axial mesoderm. Thereafter, Six9 (Optx2) is strongly expressed in the presumptive and differentiating neural retina and ventral optic stalk, in the olfactory placodes, in the hypothalamus and in the pituitary gland. This expression pattern largely overlaps with that of Six3, but several differences exist between the expression domain of the two genes. At presomitic stages, the posterior boundary of Six3 expression is at the same axial level both in the prechordal plate and in the overlying neural plate. In contrast, Six9 (Optx2) expression in the prechordal plate extends more caudal to that of the neural plate, occupying a more restricted V-shaped territory. Similarly, during the early events of eye patterning, Six3 is first expressed in the entire optic vesicle and lens placode. Only later does its expression become confined to the prospective and differentiating neural retina. Conversely, Six9 (Optx2) is never observed in the lens placode of either chick and mouse, and from early stages of optic vesicle development, Six9 (Optx2) transcripts are restrained to the prospective ventral neural retina and optic stalks.

Genomic cloning, structure, expression pattern, and chromosomal location of the human SIX3 gene.

The Drosophila gene sine oculis (so) is a nuclear homeoprotein that is required for eye development. Homologous genes to so, denoted SIX genes, have been found in vertebrates. Among the SIX genes, SIX3 is considered to be the functional homologue of so. To provide insight into the potential implications of SIX3 in human ocular malformations, we have cloned and characterized the human SIX3 gene. In human eye, SIX3 produces a 3-kb transcript that codes for a 332-amino-acid polypeptide that is virtually identical to its mouse and chick homologues. Expression of SIX3 was detected in human embryos as early as 5-7 weeks of gestation and found to be maintained in the eye throughout the entire period of fetal development. At 20 weeks of gestation, expression of SIX3 in the human retina was detected in the ganglion cells and in cells of the inner nuclear layer. The human SIX3 gene spans 4.4 kb of genomic DNA and is split in two exons separated by a 1659-bp intron. SIX3 was mapped to human chromosome 2p16-p21, between the genetic markers D2S119 and D2S288. Interestingly, the map position of human SIX3 overlaps the locations of two dominant disorders with ocular phenotypes that have been assigned to this chromosomal region, holoprosencephaly type 2 and Malattia Leventinese.