New Variants Involved in Taybi-Linder Syndrome

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.

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