elastin and Facies

Topics: Animals; Elastin; Face; Facies; Form Perception; Humans; Language; Lim Kinases; Mice; Space Perception; Williams Syndrome

Williams-Beuren syndrome (WBS) is a neurodevelopmental microdeletion disorder that usually occurs sporadically due to its location within a highly repetitive genomic region that is unstable and prone to unequal cross-over during meiosis. The consequential loss of chromosomal material includes approximately 1.5 Mb of DNA at 7q11.23. Whilst cases of dominant inheritance have been described in the literature, there have been few reports of molecular confirmation and none have carried out detailed genotyping. We describe a Bulgarian father and son with WBS detected by fluorescent in situ hybridisation (with an elastin gene probe) and loss of heterozygosity mapping using microsatellite markers located in the critical region. These individuals appear to have a common WBS heterozygous deletion, confirming the expected dominant transmission and adding to the few familial cases reported. The deletion includes the gene FKBP6 which has recently been shown to play a role in homologous chromosome pairing in meiosis and male fertility in mouse models. Homozygous Fkbp6 -/- male mice are infertile and our data suggests that haploinsufficiency for FKBP6 does not appear to preclude male fertility in WBS, although male infertility involving this gene has the potential to follow the mouse model as a human autosomal recessive condition.

Topics: Adult; Aortic Stenosis, Supravalvular; Chromosomes, Human, Pair 7; Elastin; Facies; Fathers; Gene Deletion; Gene Dosage; Genes, Dominant; Genotype; Haplotypes; Humans; Intellectual Disability; Loss of Heterozygosity; Male; Nuclear Family; Tacrolimus Binding Proteins; Williams Syndrome

Sixteen children and adolescents with a firm clinical diagnosis of Williams syndrome were investigated with the chromosome fluorescence in situ hybridisation (FISH) technique employing the elastin gene probe. In each case there was a fluorescent signal on one chromosome 7 homologue only, indicating elastin gene deletion. No deletion was demonstrated in another child in whom an earlier diagnosis of Williams syndrome was judged doubtful at review. Firm clinical diagnosis correlates with elastin gene deletion in 16/16 cases of Williams syndrome and detection of such hemizygosity by FISH constitutes a useful confirmatory diagnostic test.

Topics: Adolescent; Adult; Child; Child, Preschool; Chromosomes, Human, Pair 7; Elastin; Facies; Female; Gene Deletion; Genetic Markers; Humans; In Situ Hybridization, Fluorescence; Infant; Male; Williams Syndrome

A small pilot study has been carried out in order to assess the reliability of the detection of hemizygosity at the elastin locus by fluorescence in situ hybridisation (FISH) analysis, as a diagnostic test in both classical and atypical cases of Williams syndrome (WS). Five subjects with WS and five others in whom a diagnosis could not be confirmed on clinical criteria alone were evaluated. Hemizygosity at the elastin locus by FISH analysis was detected in all classical Williams syndrome cases and in three of the five atypical subjects. Furthermore, a combination of a few specific facial features found to be present in all subjects with the elastin gene hemizygosity has been suggested to aid the index of clinical suspicion.

Topics: Abnormalities, Multiple; Adolescent; Adult; Child; Chromosome Banding; Elastin; Facies; Female; Humans; In Situ Hybridization, Fluorescence; Male; Williams Syndrome