Mutations in the human UBR1 gene and the associated phenotypic spectrum.

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

[Neonatal computed tomographic maxillary explorations in children with unilateral cleft lip and palate]. / Etudes tomodensitométriques néonatales de l'os maxillaire dans les fentes labiopalatines unilatérales.

The aim was to examine the bony maxillary structures by computed tomographic measurements in newborns with unilateral cleft lip and palate before cheiloplasty. Analysis of maxillary bone was performed and size parameters were measured by computed-tomographic analysis in 12 infants with unilateral cleft lip and palate. We compared the bony maxillary length and the bony maxillary width between the cleft side and the healthy side. For eight patients, the bony maxillary length was different between the cleft side and the healthy side. For three patients, the bony maxillary width was different between the incisor alveolar structure in the cleft side and the healthy side. For six patients, the bony maxillary width was different between the canine alveolar structure in the cleft side and the healthy side. We noted an asymmetry without hypoplasy in bony maxillary structure in newborns before cheiloplasty. The data can serve as the starting point for a control and later evaluation on the efficiency of different therapeutic approaches of alveolar and maxillary development in children with cleft lip and palate.

Early repair for infants with cleft lip and nose.

OBJECTIVE: To study the results 10 years after early surgical cleft lip and nose repair. PATIENTS AND METHODS: We present the outcome of 123 early cleft lip repairs whose condition was managed in a multidisciplinary team according to a strict protocol. We give the observation results of operations of a single surgeon's neonatal surgery over a 10-year period in term of aesthetic assessments and dental arch relationships. One hundred and twenty-three patients were operated on during the first 4 weeks of life; a subgroup of 40 child had been operated on at a week or less of age. RESULTS: The results show good aesthetic assessments and dental relationships, with facial growth appropriate for the age. CONCLUSIONS: We are currently encouraging early cleft lip and nose repair in the full-term baby as the good method of management of newborns with cleft.