New Variants Involved in Taybi-Linder Syndrome (NewViTALS)

Identification of New Genes Involved in the Taybi-Linder Syndrome.

Taybi-Linder syndrome (TALS, OMIM 210710) is a rare autosomal recessive disorder belonging to the group of microcephalic osteodysplastic primordial dwarfisms (MOPD). This syndrome is characterized by short stature, skeletal anomalies, severe microcephaly with brain malformations and facial dysmorphism, and is caused by mutations in RNU4ATAC. Although RNU4ATAC-associated TALS is a recognizable phenotype, an atypical presentation is sometimes observed, thus expanding the clinical spectrum (TALS-like phenotype).

This study aims to identify new variants involved in Taybi-Linder syndrome and associated phenotypes (i.e.TALS-like).

This non interventional study will be performed on patients with no proven mutation of RNU4ATAC and their blood relatives (19 samples total) by high throughput sequencing and genetic analysis of already collected deoxyribonucleic acid samples.

Altogether, such a study will allow a better understanding of the molecular mechanisms responsible for the Taybi-Linder syndrome and Taybi-Linder syndrome-like phenotypes as well as the pathophysiology of these devastating forms of microcephalic dwarfism.

Study Overview

• Status: Unknown
• Conditions: Genetic Syndrome; Taybi Linder Syndrome
• Intervention / Treatment: Genetic: Deoxyribonucleic acid analysis

• Study Type: Observational
• Enrollment (Anticipated): 19

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69677
    • Service de Génétique Clinique, Groupement Hospitalier Est, Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with a Taybi-Linder or Taybi-Linder like syndrome and their blood relatives.

Description

Inclusion Criteria:

• foetus or young children diagnosed with a Taybi-Linder or Taybi-Linder like syndrome, with no RNU4ATAC mutation (index case)
• aged 20 weeks pregnant to 18 years old
• parents or sibling of the index cases, with informed consent for the analysis of both their DNA sample and the one of the index case.

Exclusion Criteria:

• no informed consent for the use of genetic samples for medical research

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Taybi-Linder index cases; Taybi-Linder index cases who have already consented for the (re)use of their DNA samples for medical research.	Genetic: Deoxyribonucleic acid analysis; This study consists in the high throughput exome sequencing and subsequent genetic bio-analysis of 19 deoxyribonucleic acid samples from 6 families, already collected and consented, including patients diagnosed with a Taybi-Linder syndrome and their relatives (parents and/or siblings).
Blood relatives of Taybi-Linder index cases; Blood relatives of Taybi-Linder index cases who have already consented for the (re)use of their DNA samples for medical research.	Genetic: Deoxyribonucleic acid analysis; This study consists in the high throughput exome sequencing and subsequent genetic bio-analysis of 19 deoxyribonucleic acid samples from 6 families, already collected and consented, including patients diagnosed with a Taybi-Linder syndrome and their relatives (parents and/or siblings).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of new variants involved in the Taybi-Linder syndrome	A genetic high throughput exome capture sequencing of 19 deoxyribonucleic acid samples from patients diagnosed with a Taybi-Linder like syndrome and their blood relatives	Collection at time of diagnosis = less than one day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2017
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 18, 2017
• First Posted (Actual): July 19, 2017

Study Record Updates

• Last Update Posted (Actual): July 19, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Endocrine System Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Fetal Diseases; Pregnancy Complications; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Growth Disorders; Bone Diseases, Developmental; Syndrome; Microcephaly; Fetal Growth Retardation; Osteochondrodysplasias; Dwarfism
• Other Study ID Numbers: 69HCL16_0774

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