# Genetic and molecular basis of hematopoietic abnormalities in ZTTK syndrome

> **NIH HL R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2026 · $508,794

## Abstract

PROJECT SUMMARY
Individuals with rare genetic diseases do not receive attention from the medical and research community. One
out of two patients diagnosed with a rare disease is a child, meaning that patients and their families must endure
long battles relating to disease progress throughout their child’s lifetime. Therefore, characterization of
clinical/molecular aspects of rare diseases will greatly benefit young patients and their families.
SON is a DNA- and RNA-binding protein that plays dual roles as an RNA splicing factor and a transcriptional
repressor. Our research team recently identified Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome), a
rare genetic disease with multi-organ abnormalities caused by heterozygous loss-of-function mutations in the
SON gene (SON haploinsufficiency). Our research and publication played a key role in documenting this
syndrome in major public databases to facilitate clinical diagnosis. As a first step in supporting ZTTK families
and promoting awareness, we recently launched an official foundation, the ZTTK SON-Shine Foundation.
Our recent efforts revealed that many children with ZTTK syndrome experience various hematopoietic disorders
and immune dysfunction, which sometimes leads to life-threatening sepsis. To understand the hematopoietic
abnormalities associated with ZTTK syndrome, we have generated mouse models of Son knockout (KO) and
Son haploinsufficiency. Our preliminary data demonstrated that complete Son KO in hematopoietic cells causes
hematopoietic stem cell (HSC) expansion and embryonic lethality. Furthermore, we found that Son
haploinsufficiency leads to abnormal proportions of lineage-primed multipotent progenitors (MPPs), with an
expansion of megakaryocyte-erythroid lineage-primed MPPs and a shrinkage of lymphoid lineage-primed MPPs,
which is already evident during fetal liver hematopoiesis and persists in adult hematopoiesis in the bone marrow.
Importantly, our RNA-sequencing analyses revealed that critical chro

## Key facts

- **NIH application ID:** 11251965
- **Project number:** 5R01HL168659-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Erin Eun-Young Ahn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $508,794
- **Award type:** 5
- **Project period:** 2023-03-15T00:00:00 → 2026-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11251965

## Citation

> US National Institutes of Health, RePORTER application 11251965, Genetic and molecular basis of hematopoietic abnormalities in ZTTK syndrome (5R01HL168659-04). Retrieved via AI Analytics 2026-07-15 from https://api.ai-analytics.org/grant/nih/11251965. Licensed CC0.

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