# Functional Analysis of Whole Exome Sequence Variants Identified in Patients with Vertebral Malformations

> **NIH NIH R03** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $137,000

## Abstract

Vertebral malformations (VMs) represent conditions that occur with an estimated incidence of
1/2000 and pose a significant public health impact due to their association with congenital
scoliosis (CS) and other conditions. In order to better understand genetic variants that contribute
to VM, we propose to perform whole exome sequence analysis (WES) in 86 patients with VM
through the Baylor Hopkins Center for Mendelian Genetics and Victor Chang Cardiac Research
Institute. Following rigorous bioinformatics analysis sequence variants have been identified so
far in COL11A2. To determine the requirement for col11a2 in vertebral development, we will
employ established CRISPR/Cas9 gene targeting approaches to generate zebrafish col11a2
loss-of-function (LOF) and VM-associated alleles. Caudal vertebral fusions have been observed
in our laboratory in stable F2 col11a2 LOF mutants, which supports a role for col11a2 in
vertebral development. To investigate the functional consequence and pathogenicity of
COL11A2 R130W, R1407H, and R1413H VM-associated mutations, we will employ 2 parallel
genetic strategies: (1)Create CRISPR/Cas9-based knock-in (KI) mutations; (2)Rescue LOF
phenotypes with VM-associated col11a2 expression transgenes. The ability to identify genes
associated with VM will serve as a foundation for classification of VM which can then be used
identify novel pathways, novel phenotypes associated with patterning gene mutations, and to
guide prevention and therapeutic strategies for patients cared for by the clinical genetics and
greater pediatric orthopedic community.

## Key facts

- **NIH application ID:** 10349921
- **Project number:** 7R03HD099516-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Philip F Giampietro
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $137,000
- **Award type:** 7
- **Project period:** 2020-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10349921

## Citation

> US National Institutes of Health, RePORTER application 10349921, Functional Analysis of Whole Exome Sequence Variants Identified in Patients with Vertebral Malformations (7R03HD099516-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10349921. Licensed CC0.

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