Delineating the Molecular Spectrum and the Clinical, Imaging and Neuronal Phenotype of Chopra-Amiel-Gordon Syndrome

NCT05528744 | Recruiting

• 1 other identifier: P00041124
• Study Type: observational
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to establish the longitudinal natural history of individuals with confirmed or suspected Chopra-Amiel-Gordon Syndrome (CAGS) to learn more about the range of symptoms, changes in the structure of the brain seen on imaging, and learning difficulties that individuals with this disorder may experience. The investigators will obtain medical history, family history, MRI records, patient photographs, genetic test results, neurobehavioral and quality of life questionnaires from individuals with confirmed or suspected CAGS at annual research visits. Participants may also complete standardized research neurobehavioral assessments, research EEGs, and sample collections at each visit. This data will be maintained on a secure research database. Samples collected will be used for functional testing and the generation of iPSC cell lines, for neuronal reprogramming and phenotyping.

Conditions

Genetic Disease; Chopra-Amiel-Gordon Syndrome; CAGS; ANKRD17

Keywords

Syndrome; Neurodevelopmental; ANKRD17 Loss of function; ANKRD17; Rare Disease; CAGS; Chopra-Amiel-Gordon

Outcome Measures

Primary Outcomes (2)

• Research registry of molecular and phenotypic information related to CAGS

  The primary endpoint of this cross-sectional natural history study will be the creation and implementation of a research registry of molecular and phenotypic information for CAGS.

  4-5 years

• Generation of patient-derived iPSC cell lines

  An additional objective of this cross-sectional natural history study will be the generation of patient-derived iPSC cell lines. iPSC cell lines will be created from blood and skin samples of individuals with ANKRD17 variants, using samples from unaffected family members as controls.

  4-5 years

Study Arms (2)

Proband

Study participants who have suspected or confirmed CAGS based on having a variant of uncertain significance, likely pathogenic variant, or pathogenic variant in ANKRD17 and clinical features of the condition.

Other: Observational Study

Unaffected family members

Family members of the proband who do not have an ANKRD17 variant.

Other: Sample collection only

Interventions

Observational Study OTHER

No intervention. This is an observational study

Proband

Sample collection only OTHER

Collection of blood and/or skin samples.

Unaffected family members

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients of all ages and genders with a variant in ANKRD17 confirmed by pre-existing clinical genetic testing

You may qualify if:

• Participants must have a variant in ANKRD17 with a classification of VUS, likely pathogenic, or pathogenic
• Participants with a known diagnosis or CAGS have a disease-causing (likely pathogenic or pathogenic) variant in ANKRD17 evidenced by a pre-existing clinical genetic report.
• Participants with a suspected diagnosis of CAGS must have a variant of uncertain significance in ANKRD17 evidenced by a pre-existing clinical genetic report and clinical features of CAGS
• Participants with a VUS in ANKRD17 must have a variant of uncertain significance in ANKRD17

You may not qualify if:

• No evidence of a disease-causing or potentially disease-causing variant ANRKD17 variant on a pre-existing clinical genetic report.

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (2)

• Sveden A, Gordon CT, Amiel J, Chopra M. ANKRD17-Related Neurodevelopmental Syndrome. 2022 Dec 22. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK588029/

  PMID: 36548456 BACKGROUND

• Chopra M, McEntagart M, Clayton-Smith J, Platzer K, Shukla A, Girisha KM, Kaur A, Kaur P, Pfundt R, Veenstra-Knol H, Mancini GMS, Cappuccio G, Brunetti-Pierri N, Kortum F, Hempel M, Denecke J, Lehman A; CAUSES Study; Kleefstra T, Stuurman KE, Wilke M, Thompson ML, Bebin EM, Bijlsma EK, Hoffer MJV, Peeters-Scholte C, Slavotinek A, Weiss WA, Yip T, Hodoglugil U, Whittle A, diMonda J, Neira J, Yang S, Kirby A, Pinz H, Lechner R, Sleutels F, Helbig I, McKeown S, Helbig K, Willaert R, Juusola J, Semotok J, Hadonou M, Short J; Genomics England Research Consortium; Yachelevich N, Lala S, Fernandez-Jaen A, Pelayo JP, Klockner C, Kamphausen SB, Abou Jamra R, Arelin M, Innes AM, Niskakoski A, Amin S, Williams M, Evans J, Smithson S, Smedley D, de Burca A, Kini U, Delatycki MB, Gallacher L, Yeung A, Pais L, Field M, Martin E, Charles P, Courtin T, Keren B, Iascone M, Cereda A, Poke G, Abadie V, Chalouhi C, Parthasarathy P, Halliday BJ, Robertson SP, Lyonnet S, Amiel J, Gordon CT. Heterozygous ANKRD17 loss-of-function variants cause a syndrome with intellectual disability, speech delay, and dysmorphism. Am J Hum Genet. 2021 Jun 3;108(6):1138-1150. doi: 10.1016/j.ajhg.2021.04.007. Epub 2021 Apr 27.

  PMID: 33909992 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Human blood and skin samples for repository and the establishment of iPSC lines.

MeSH Terms

Conditions

Genetic Diseases, Inborn; Syndrome; Rare Diseases

Interventions

Observation

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Maya Chopra, MBBS, FRACP

  Boston Children's Hospital

  STUDY CHAIR

Central Study Contacts

Abigail Sveden, MS, CGC

CONTACT

617-919-5214; Abigail.sveden@childrens.harvard.edu

Jillian O'Toole, MS, CGC

CONTACT

jillian.otoole@childrens.harvard.edu

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Translational Genomic Medicine, Rosamund Stone Zander Translational Neuroscience Centre at Boston Children's Hospital

Study Record Dates

• First Submitted: May 3, 2022
• First Posted: September 6, 2022
• Study Start: August 27, 2022
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)