ABSTRACT
Introduction: Townes-Brocks syndrome (TBS), a rare autosomal dominant genetic condition associated with SALL1 (Spalt like Transcription Factor 1), is reported to be present in 1:238,000 individuals in the general population. TBS is characterized by the triad of anorectal malformations, dysplastic ears, with or without hearing impairment, and hand or thumb anomalies. Although kidney involvement is less common in TBS, the disease can progress to kidney failure. Here, we sought to characterize the incidence of SALL1 variants in individuals undergoing broad-based genetic testing with a kidney gene panel and to quantify the presence of (extra)renal features. Methods: A retrospective analysis of the genetic data from a 385-gene panel identified cases with a pathogenic (P) or likely pathogenic (LP) variant in SALL1. Data including age, features, and disease progression were collected. Results: Of 35,044 samples, P or LP variants in SALL1 were identified in 22, yielding a prevalence of 1:1592 among patients tested for monogenic kidney disease, and 1:342 among cases identified with a monogenic kidney disease. Among this cohort, the median patient age was 23 years (range: 3 months-62 years) with chronic kidney disease (CKD) reported in 91% (20/22) of cases. Reported kidney features included renal agenesis/hypoplasia (7/22; 32%), focal segmental glomerulosclerosis (4/22; 18%), and kidney cysts (3/22; 14%). Confirmed extrarenal features included hearing loss and/or ear features (7/22; 32%), anorectal malformations (6/22; 27%) and hand or thumb abnormalities (4/22; 18%). Three patients (3/22; 14%) had both a priori TBS diagnoses and the traditional "triad." Conclusion: Traditionally, a molecular diagnosis was ascertained primarily in individuals presenting with cardinal features of TBS; therefore, individuals with mild or atypical presentations were often overlooked clinically. Our findings reveal that SALL1 P/LP variants could be a consequential contributor to monogenic kidney disease.
ABSTRACT
The Pekin duck is a valuable agricultural commodity globally and in the United States. Pekin ducks are seasonal breeders; they are sensitive to light and thus, research on the neuroendocrine and behavioral responses are needed to maximize production and to improve their welfare. There is compelling evidence that specific wavelengths of light may adversely alter the growth and welfare of meat (grow out) ducks. However, despite a birds' dependence upon light, in commercial poultry hatcheries, incubators almost exclusively hold eggs in the dark. Therefore, our objective was to determine the effects of lighting on the expression of retina photoreceptors (RPs) and deep brain photoreceptors (DBPs) during duck embryological development. Two groups of ducks were raised with and without light over 21 d from egg laying, embryonic day 0. Brain and retinal tissues were collected at embryonic days 3, 7, 11, 16, and 21 of a 24 d incubation period. qRT-PCR was performed on RPs (OPN1LW, OPN2SW, OPN1SW, MAFA, RHO, and RBP3) and the DBP OPN4M from retinal and brain samples, respectively. We find that the presence and absence of light during pre-hatch incubation, had no influence on the expression of any retinal photoreceptor. However, a late embryological increase in DBP OPN4M expression was observed. Taken together, the impact of light during pre-hatch incubation does not impact the overall post-hatch production. However, future directions should explore how OPN4M pre-hatch activation impacts Pekin duck post-hatch development and growth.
