RESUMEN
Autosomal recessive osteopetrosis is a severe hereditary bone disease whose cellular basis is in the osteoclast, but with heterogeneous molecular defects. We hereby report the clinical and the molecular study of seven patients affected by the recessive form of osteopetrosis (ARO) from six families originating from the Middle-East: four from Lebanon and two from Syria. Parental consanguinity was found in five families. The mean age of diagnosis was 3 months. Failure to thrive, prominent forehead, exophthalmia, optic atrophy, hepatosplenomegaly, neurological manifestations, anaemia, thrombocytopenia, hypocalcaemia, elevated hepatic enzymes and acid phosphatase, and an early fatal outcome were common. Macrocephaly, strabismus, and brain malformations were relatively less common. Mutations were identified in two genes: TCIRG1 and OSTM1. Phenotype-genotype correlation is discussed.
Asunto(s)
Osteopetrosis/genética , Secuencia de Bases , Consanguinidad , Análisis Mutacional de ADN , Cartilla de ADN/genética , Exones , Femenino , Genes Recesivos , Genotipo , Humanos , Lactante , Líbano , Masculino , Proteínas de la Membrana/genética , Mutación , Osteopetrosis/enzimología , Linaje , Fenotipo , Empalme del ARN/genética , Siria , Ubiquitina-Proteína Ligasas/genética , ATPasas de Translocación de Protón Vacuolares/genéticaRESUMEN
We report on a baby girl from non-consanguineous Palestinian parents with intrauterine growth retardation, low birth weight, and developmental delay. She had a short stature, microcephaly, a prominent metopic suture, a glabellar haemangioma, exophthalmos, hypertelorism, upslanting palpebral fissures, horizontal nystagmus, flat nose, cleft lip and palate, a short neck, widely spaced nipples, umbilical hernia, flexion deformity of the wrist, ulnar deviation of fingers, and right club foot. Cortical atrophy, enlarged ventricles, a thin corpus callosum, thoracic hemivertebrae, and a ventricular septal defect were detected as well. High resolution chromosome analysis identified in 92% of cells an isochromosome 18 and in 8% of cells a ring 18. Molecular cytogenetic investigations confirmed that it was an i(18q) and a r(18q). The hypothesis to account for this anomaly and its corresponding phenotype are discussed.
Asunto(s)
Anomalías Múltiples/genética , Cromosomas Humanos Par 18/genética , Isocromosomas/genética , Mosaicismo , Cromosomas en Anillo , Anomalías Múltiples/patología , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/patología , Análisis Citogenético , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Femenino , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/patología , Humanos , Hibridación Fluorescente in Situ , Lactante , Modelos Genéticos , Fenotipo , Intercambio de Cromátides HermanasRESUMEN
Monozygotic twin brothers are described who share clinical features which include: moderate mental retardation, short stature, macrocephaly, frontal bossing, ptosis, low-set ears, brachydactyly, 5th fingers clinodactyly, single palmar creases, cryptorchidism, and prelingual sensorineural deafness. One of the twins presented with mild cardiac dilatation and died at age 3(1/2) from cardiac arrest during an episode of acute respiratory infection. While chromosome analyses performed for both twins on peripheral blood showed apparently normal karyotypes, screening for all telomeric regions on the surviving propositus revealed a combination of partial 6p trisomy and partial 11q monosomy. A balanced reciprocal translocation was found in the father. The phenotype of the twins is most likely related to this cryptic chromosomal rearrangement. The fact that the phenotype in this family partially overlaps with some previously reported phenotypes is discussed.