# Contributions of sex chromosomal gene homologues to X monosomy

> **NIH NIH R01** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $398,750

## Abstract

Turner syndrome (TS) results from 45,X karyotype (XO), which is both the most common aneuploidy in
utero (1.5%) and the single most frequent cause (~15%) of spontaneous termination. In addition to this
dominant prenatal burden, TS individuals (1 in 2000 live births) suffer from short stature as well as cognitive,
renal and serious cardiovascular defects. The latter span congenital heart defects and improper aortic
development, which elevate the risk of fatal aortic events by almost two orders of magnitude over the general
population. Collectively, cardiovascular malformations alone shorten life expectancy in the TS cohort by over a
decade.
 Understanding the exact developmental-genetic etiology of TS is fundamental to better predicting and
possibly addressing such adverse outcomes. However, neither TS-associated heart and aortic defects, nor the
high termination rate of X monosomy have been mapped to specific genes to-date. Our central hypothesis is
that TS results from a haploinsufficiency in a subset of homologous genes that are encoded on both sex
chromosomes. The objectives of this application are to quantify the gene dosage impact of the second sex
chromosome (Y or inactive X) on human induced pluripotent stem cells (hiPSCs) and differentiated smooth
muscle cells (SMCs), and to narrow in on a subset of X-Y gene pairs relevant to SMC development and
function. We have established otherwise isogenic hiPSCs from individuals that were mosaic for the presence
of the second sex chromosome. We will compare hiPSC and SMC gene expression and differentiation
potential while excluding the impact of genetic variation, and utilize both induced segmental and gene-specific
deletions to dissect contributions of X-Y gene pairs. These hiPSC and derived SMC panels will enable us to
identify cellular traits, genes and pathways sensitive to the presence and identity of the second sex
chromosome, and help to uncover their possible impact on X monosomy and Turner syndrome.
.

## Key facts

- **NIH application ID:** 10130599
- **Project number:** 5R01HL141324-04
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Stefan F. Pinter
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $398,750
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130599

## Citation

> US National Institutes of Health, RePORTER application 10130599, Contributions of sex chromosomal gene homologues to X monosomy (5R01HL141324-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10130599. Licensed CC0.

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