Natural History Study of GEMIN-5 Related Neurodevelopmental Disorder

Retrospective and Longitudinal Prospective Natural History Study of GEMIN5-Related Neurodevelopmental Disorder

This study will include a comprehensive retrospective chart review and a longitudinal prospective observational natural history study to characterize the phenotypic spectrum of GEMIN5-Related Neurodevelopmental Disorder. We aim to define the trajectory of this ultra-rare disease, core clinical features, characteristics at disease onset and diagnosis, neurological symptomatology, and neuroimaging findings over time. In this study, biological specimens (serum) will also be collected in a biorepository for translational research purposes.

Study Overview

• Status: Recruiting
• Conditions: Neurodevelopmental Disorders; SMN Complex Proteins; GEMIN5 Protein, Human
• Intervention / Treatment: Other: GEMIN5-Related Neurodevelopmental Disorder

Detailed Description

This study will include individuals across the lifespan with molecularly confirmed GEMIN5 biallelic mutations.

This study will be ongoing indefinitely.

There are three main components to the study as are detailed below:

1. A retrospective chart review of UPMC medical records and other institutions' medical records, for all patients in the study. Families/patients will provide staff with a signed Release of Information, so that we can obtain a copy of the participants complete medical record which will be requested from previously treating physicians. This may include records from several disciplines, for example neurological and physical exams, neurodevelopmental testing (cognitive, motor, language and daily living skills), growth parameters, results to previous genetic testing, MRI, lab results including lumbar puncture studies, audiologic exam, vision screening, nerve conduction studies, ophthalmologic exam, swallow studies, co-morbidities, and family history.
2. An observational, longitudinal prospective study of patients seen at the UPMC Center for Neuogenomics (CCNG) clinic. Clinical data obtained as part of a typical CCNG visit include vital signs, measurements (weight, head circumference, length), a developmental history, neurodevelopmental testing (eg. cognitive, speech and language, motor skills, developmental skills, vision, hearing), and a comprehensive neurological exam, including an ataxia rating scale. Additionally, any neurodiagnostic results obtained clinically are reviewed if available, such as MRI brain and spine, EEG, and nerve conductions studies.
3. Patients who are seen at the CCNG clinic in person may opt to submit an optional research biological samples.

Primary endpoint:

Neurodevelopmental outcomes

Secondary endpoint (if available):

MRI - presence of cerebellar atrophy Survival Vision Hearing Biomarkers of disease

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Kate Kielty, MD; Phone Number: 412-692-6350; Email: CCNG@chp.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • Children's Hospital of Pittsburgh of UPMC
      • Contact: Kate Kielty, MD; Phone Number: 412-692-6350; Email: CCNG@chp.edu
      • Sub-Investigator: Deepa Soundara Rajan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Individuals with GEMIN5-Related Neurodevelopmental Disorder

Description

Inclusion Criteria:

• Individuals with molecularly confirmed GEMIN5 biallelic mutations, ages 0 years and above

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

GEMIN5

Other: GEMIN5-Related Neurodevelopmental Disorder; This is an observational study. The investigators will collect data from participants' medical records regarding neurodevelopmental outcomes (eg. cognitive, speech and language, motor skills, developmental skills, vision, hearing), Time to event (Acquistion and loss of developmental milestones), and, if available, data regarding MRIs (presence of cerebellar atrophy), survival, visiion, hearing, and biomarkers of disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
neurodevelopmental outcomes	time to acquisition and/or loss of milestones	26 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI	presence of cerebellar atrophy	26 years
Survival	age at death	26 years
Vision	presence of ocular pathology	26 years
Hearing	presence of hearing loss	26 years
Biomarkers of disease	Biomarkers of disease	26 years

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Kate Kielty, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2025
• Primary Completion (Estimated): December 1, 2050
• Study Completion (Estimated): December 1, 2050

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 9, 2025
• First Posted (Actual): January 15, 2025

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Neurodevelopmental Disorders; GEMIN5
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders
• Other Study ID Numbers: STUDY24060013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No