A genetic marker of the ACKR1 gene is present in patients with Type II congenital smell loss who have type I hyposmia and hypogeusia

Abstract

PURPOSE Our previous study of Type II congenital smell loss patients revealed a statistically significant lower prevalence of an FY (ACKR1, formerly DARC) haplotype compared to controls. The present study correlates this genetic feature with subgroups of patients defined by specific smell and taste functions. METHODS Smell and taste function measurements were performed by use of olfactometry and gustometry to define degree of abnormality of smell and taste function. Smell loss was classified as anosmia or hyposmia (types I, II or III). Taste loss was similarly classified as ageusia or hypogeusia (types I, II or III). Based upon these results patient erythrocyte antigen expression frequencies were categorized by smell and taste loss with results compared between patients within the Type II group and published controls. RESULTS Comparison of antigen expression frequencies revealed a statistically significant decrease in incidence of an Fyb haplotype only among patients with type I hyposmia and any form of taste loss (hypogeusia). In all other patient groups erythrocyte antigens were expressed at normal frequencies. CONCLUSIONS Data suggest that Type II congenital smell loss patients who exhibit both type I hyposmia and hypogeusia are genetically distinct from all other patients with Type II congenital smell loss. This distinction is based on decreased Fyb expression which correlated with abnormalities in two sensory modalities (hyposmia type I and hypogeusia). Only patients with these two specific sensory abnormalities expressed the Fyb antigen (encoded by the ACKR1 gene on the long arm of chromosome 1) at frequencies different from controls.

Initiation of smell function in patients with congenital hyposmia

“…Type II represents 88% of patients [1,2]. They do not have a family history of smell loss and do not have significant brain, somatic or defined genetic abnormalities [1,2,5]. Despite these differences, both types have similar degrees of loss of smell function [1,2,5].…”

“…These designations have been used for the past 32 years. Each designation has a physiological and pathological basis which has been carefully delineated previously [1,5,6,10].…”

“…One patient had anosmia, 15 patients had type I hyposmia and three patients had type II hyposmia [5,6]. The anosmic patient was a woman.…”

“…We have extensively studied patients with Type II congenital hyposmia [1,2,5] including a report which described localization of a potential genetic abnormality on chromosome 1 [2,5]. In these and other studies we evaluated smell function using both subjective responses [6,7] and olfactometry [6,7] to measure smell function before and after treatment with the oral phosphodiesterase inhibitor theophylline [6,7] which initiated smell function in many groups of patients with various types of smell loss [6,7] including some with Type II congenital hyposmia.…”