Date of Award

12-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Healthcare Genetics

Committee Chair/Advisor

Dr. Sara Sarasua

Committee Member

Dr. Jane DeLuca

Committee Member

Dr. Luigi Boccuto

Committee Member

Dr. Stephanie Davis

Abstract

This dissertation dives into a rare genetic disorder, Phelan-McDermid syndrome (PMS). PMS is a neurodevelopmental disorder caused by a terminal deletion of chromosome 22q13.3 or SHANK3 pathogenic variants. Along with neurodevelopmental disorders, the literature indicates patients with PMS present with kidney disorders with rates as high as 40% in those with 22q13.3 including interstial deletions and up to 37% in those with 22q13.3 with terminal deletions. There is limited research on renal disorders in patients with PMS, therefore, we reviewed the literature to determine what types of kidney disorders were present. Most published studies had small sample sizes, hampering definitive investigations. The identified PMS cases were pooled to create a large cohort of patients with known chromosome 22 breakpoints and status of kidney disorder diagnoses. The cohort was analyzed for genomic regions significantly associated with renal disorders to determine potential candidate genes for kidney disorders in PMS. The Phelan-McDermid Syndrome Foundation International Registry was used to validate the previous results. Based on this dissertation, we identify WNT7B, UPK3A, FBLN1, CELSR1, PPARA, TRMU, ZBED4, MLC1, PLXNB2, TYMP, and ARSA as candidate genes for Kidney disorders in PMS that merit follow-up studies. Diagnoses and treatment for kidney disorders can be challenging in patients with PMS due to the high rate of co-occurring neurodevelopmental disorders in these individuals. They are not able to always communicate pain or discomfort. Therefore, finding candidate genes for kidney disorders could lead to earlier diagnoses of kidney disorders in patients with PMS, allowing for faster treatment.

Available for download on Thursday, December 01, 2022

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