Nine novel mutations in NR0B1 (DAX1) causing adrenal hypoplasia congenita.

X-linked adrenal hypoplasia congenita (AHC) is caused by mutations in the NR0B1 gene. This gene encodes an orphan member of the nuclear receptor superfamily, DAX1. Ongoing efforts in our laboratory have identified nine novel NR0B1 mutations in X-linked AHC patients (Y81X, 343delG, 457delT, 629delG, L295P, 926-927delTG, 1130delA, 1141-1155del15, and E428X). Two additional families segregate previously identified NR0B1 mutations (501delA and R425T). Sequence analysis of the mitochondrial D-loop indicates that the 501delA family is unrelated through matrilineal descent to our previously analyzed 501delA family.

Uruguay facio-cardio-musculo-skeletal syndrome: a novel X-linked recessive disorder.

We report on three male patients from a single family with a brachyturricephaly, "pugilistic" facial appearance, a muffled voice, cardiomyopathy, muscular hypertrophy, broad hands, wide feet with progressive pes cavus deformities, dislocation of toes, variable congenital hip dislocation, and scoliosis. Three other males in the family, now deceased from cardiac disease, appear to have had the same disorder. The mother of the propositus has milder signs of the syndrome. All affected males are related through the maternal line. These cases represent an apparently previously undescribed X-linked recessive syndrome.

Visual acuity in infants and children with Down syndrome.

The authors used the Teller acuity cards to assess the visual acuity of 51 infants and children with Down syndrome aged between two months and 18 years. The success rate and test times were comparable to those reported for normally developing children. Even those subjects in the study who were free of ocular disorders and/or who were wearing optical correction during testing showed significantly poorer visual acuity than individuals without Down syndrome. The development of visual acuity in infants and children with Down syndrome lags behind that of age-matched peers without Down syndrome, especially after the age of six months. These findings are discussed in terms of the neurological and optical factors that might account for the deficits in visual acuity that were observed.

Van der Woude syndrome. A case report.

We describe several members of a family with Van der Woude syndrome, a genetic and congenital malformation syndrome with autosomal dominant inheritance and 70% to 80% penetrance with variable expressivity. It is characterized by clinical signs localized to the face, such as bilateral or unilateral pits on conical elevations in babies or extensive depressions in adults, both in the vermilion border of the lower lip, with cleft lip, with or without cleft palate and uvula. Small accessory or heterotopic salivary glands empty into sinuses or fistulas in the lips. This eight member family had various clinical signs of the condition. All had cleft lip and palate. We studied the major characteristics of the eight patients and describe histopathologic and immunohistochemical features.

Experiencia metodológica en pesquisa neonatal de hiperfenilalaninemias. Instituto de Genética Médica del Hospital Italiano / Newborn screening for hyperphenylalanine. Institute of Medical genetics of Hospital Italiano

La detección neonatal de errores congénitos del metabolismo mediante pesquisa neonatal consiste en la búsqueda sistemática en el recién nacido de aquellas afecciones para las que existe un tratamiento probadamente efectivo ante su instalación precoz. En el Instituto de Genética Médica del Hospital Italiano se realiza, desde noviembre de 1993, la cuantificación de fenilalanina sanguínea en el recién nacido en sangre seca sobre papel de filtro mediante método fluorométrico como test de pesquisa para hiperfenilalaninemias. Los reactivos son preparados en el laboratorio y la exactitud del método es controlada a través de un programa de control de calidad externo por método de referencia. En el presente trabajo se estimó el valor de un punto de corte en función del cual considerar un resultado como presuntamente positivo para nuestra población (n=190), obteniéndose un valor de 2,5 mg/dl de fenilalanina. Se evaluó el método fluorométrico utilizado. El análisis de regresión entre los resultados obtenidos por el método en uso y el de referencia mostró que existe asociación lineal entre estos resultados (n=93; r=0,94; y=0,87x + 0,519) y que aunque ambos métodos no son intercambiables, sí son equivalentes, lo cual otorga confianza al método en uso. Se examinó la estabilidad de la Phe en muestras de sangre recogidas sobre papel de filtro almacenadas a 4°C. El porcentaje del aminoácido recuperado después de 5 años de almacenamiento (83 por ciento a 100 por ciento) y el test estadístico aplicado mostraron que el aminoácido tiene buena estabilidad almacenando las muestras en esas condiciones.