Candidate loci for Zimmermann–Laband syndrome at 3p14.3

Abstract

A male with 46,XY,t(3;17)(p14.3;q24.3) presented with gingival hyperplasia, hypertrichosis, unusually large ears and marked hypertrophy of the nose, characteristic of the Zimmermann-Laband syndrome (ZLS). Other features include large facial bones and mandibles, large protruding upper lip, enlarged fingers and toes, strabismus, and enlarged phallus. Knowledge of a 46,XX,t(3;8)(p21.2;q24.3) reported previously in a mother and daughter with ZLS suggests that the 3p14.3-p21.2 region may contain a gene responsible for ZLS. We have reassessed the chromosome 3 breakpoint region of the t(3;8) and revised its breakpoint location to 3p14.3, based upon an updated human genome sequence assembly. Using fluorescence in situ hybridization (FISH) with BAC clones, we have also identified a breakpoint spanning clone at 3p14.3 in our t(3;17) patient, thereby narrowing the breakpoint to a region of approximately 200 kb. These data suggest that the gene responsible for ZLS is located in 3p14.3 and implicates four likely candidate genes in this region: CACNA2D3, encoding a voltage-dependent calcium channel, LRTM1, a gene of unknown function embedded within CACNA2D3, WNT5A, encoding a secreted signaling protein of the WNT family, and ERC2, which codes for a synapse protein.

Extensive molecular genetic analysis of the 3p14.3 region in patients with Zimmermann–Laband syndrome

“…The occurrence of a 3;8 translocation in mother and daughter, both of which presented with the typical features of ZLS, further supports this mode of inheritance [Stefanova et al, 2003]. Breakpoint mapping of a de novo 3;17 translocation in a male with features characteristic of ZLS indicated that the 3p14.3 breakpoint of both cases may be shared, suggesting that a gene causative for ZLS is located in this region [Kim et al, 2007]. By fluorescence in situ hybridization (FISH) analysis, one BAC clone was found to span the 3p14.3 breakpoint of the t(3;17), thereby directly disrupting the CACNA2D3 gene [Kim et al, 2007].…”

“…Breakpoint mapping of a de novo 3;17 translocation in a male with features characteristic of ZLS indicated that the 3p14.3 breakpoint of both cases may be shared, suggesting that a gene causative for ZLS is located in this region [Kim et al, 2007]. By fluorescence in situ hybridization (FISH) analysis, one BAC clone was found to span the 3p14.3 breakpoint of the t(3;17), thereby directly disrupting the CACNA2D3 gene [Kim et al, 2007]. CACNA2D3 encodes the auxiliary α2δ‐3 subunit part of the voltage‐gated Ca 2+ channel which is implicated in a wide range of physiological processes [Felix, 2006].…”

Epigenetic regulation of estrogen receptor beta expression in the rat cortex during aging

“…Genomic DNA was extracted from the cortex of young and middle-aged female rats (n = 6–8), as described above. Pyrosequencing was performed by EpigenDx, as previously described [21]. Briefly, sodium bisulfite modification was conducted on the genomic DNA.…”

Impaired FGF signaling contributes to cleft lip and palate

“…Two mutations in the FGFR2 gene, S252W and P253R, account for almost all cases of Apert syndrome; the clefting phenotype is more commonly associated with the S252W mutation (59%) than with the P253R mutation (17%) (12,14). The autosomal-dominant KS, whose main features are anosmia and hypogonadotrophic hypogonadism, is caused by loss-of-function mutations in FGFR1, and 5-10% of these patients have a cleft (unpublished estimate) (15)(16)(17). Additionally, mutations in FGF10 are associated with autosomal-dominant aplasia of lacrimal and salivary glands (18).…”