Product Description:
We describe a family with an 18q22.3-q23 interstitial deletion and corresponding clinical features of the 18q22-qter deletion syndrome. The clinical phenotype of the proband and two maternal half-siblings includes short stature, a seizure disorder, developmental delays, hearing loss, and aural atresia with clefting of the soft palate. The deletion was initially identified by BAC aCGH followed by confirmatory FISH studies. Precise definition of the breakpoints was achieved by using oligonucleotide aCGH which redefined the minimum region of deletion as a 4.1 megabase interstitial deletion at 18q22.3-q23, from linear location 70565916bp - 74719434bp (hg18). The previously defined region associated with the cleft palate component in the 18q22.3-qter deletion syndrome has been reported to be 7.2 megabases, our study has helped refine this minimum deleted region. There are nine genes located in the deleted region, and two of them are strong candidates that might account for at least three of the observed anomalies. We assert that a strong candidate gene for two of these anomalies, cleft palate and congenital aural atresia, is teashirt zinc finger-1 (TSHZ1), an evolutionarily conserved putative zinc finger transcription factor. Galanin receptor-1 (GALR1), a receptor for the neuropeptide galanin, could be considered a candidate for seizures in these patients and may explain the association of epilepsy with 18q deletion syndrome. Oligonucleotide aCGH more accurately defines the breakpoints while identifying the specific genes involved in chromosomal deletions. Particularly in this familial study, the use of oligonucleotide aCGH facilitated precise phenotype/genotype correlations and has helped refine the minimum deleted region associated with 18q deletion syndrome. Our study underscores the importance of using high resolution aCGH in clinical investigations for accurate definition of the genetic anomaly and help gain a better understanding of the functional role of specific genes located within the critical regions.
