Jacobsen Syndrome: Surgical Complications due to Unsuspected Diagnosis, the Importance of Molecular Studies in Patients with Craniosynostosis.

Jacobsen syndrome (JBS) is an uncommon contiguous gene syndrome. About 85-92% of cases have a de novo origin. Clinical variability and severity probably depend on the size of the affected region. The typical clinical features in JBS include intellectual disability, growth retardation, craniofacial dysmorphism as well as craniosynostosis, congenital heart disease, and platelet abnormalities. The proband was a 1 year/3-month-old Mexican male. Oligonucleotide-SNP array analysis using the GeneChip Human Cytoscan HD was carried out for the patient from genomic DNA. The SNP array showed a 14.2-Mb deletion in chromosome 11q23.3q25 (120,706-134,938 Mb), which involved 163 RefSeq genes in the database of genomic variation. We report a novel deletion in JBS that increases the knowledge of the variability in the mutation sites in this region and expands the spectrum of molecular and clinical defects in this syndrome.

Discordant retinoblastoma in monozygotic twins due to deletion of 13q14.

PURPOSE: To report discordant retinoblastoma in monozygotic twins, confirmed by GeneScan. METHODS: One twin presented unilateral retinoblastoma that was treated with enucleation; the other twin had no retinoblastoma. To confirm monozygosity, DNA from leukocytes was analyzed through GeneScan with highly polymorphic markers; to exclude 13q14 deletion, FISH analysis was performed in leukocytes and oral cells of both twins and their parents and in retinal tissue of the affected twin with the cDNA LSI RB1 probe. RESULTS: GeneScan analysis confirmed monozygosity. 13q14 deletion was observed in homozygous state in retinal tissue and in heterozygous state in oral cells and leukocytes of the affected twin. The nonaffected twin and parents showed no deletion of 13q14. CONCLUSIONS: These data show unexpected differences in monozygotic twins that could be explained by postzygotic events in embryonic development.

A family with autosomal dominant primary congenital cataract associated with a CRYGC mutation: evidence of clinical heterogeneity.

PURPOSE: To describe a family with primary congenital cataract associated with a CRYGC mutation. METHODS: One family with several affected members with primary congenital cataract and 170 healthy controls were examined. DNA from leukocytes was isolated to analyze the CRYGA-D gene cluster. RESULTS: DNA sequencing analysis of the CRYGA-D gene cluster of the affected members showed the heterozygous missense mutation c.502C>T in the CRYGC gene. This transition mutation resulted in the substitution of Arg at position 168 by Trp. Analysis of the healthy members of the family and 170 unrelated controls showed a normal sequence of the CRYGA-D gene cluster. CONCLUSIONS: In the present study, we described a family with nuclear congenital cataract that segregated the CRYGC missense mutation c.502C>T. This mutation has been associated with the phenotype of lamellar cataract but is also considered a single nucleotide polymorphism (SNP) in the NCBI database. Our data and previous report support that R168W is the actual disease-causing mutation and should no longer be considered a SNP. This is the first case of phenotypic heterogeneity in the primary congenital cataract specifically associated with the R168W mutation in the CRYGC gene.