Genetic and Clinical Insights into Alazami Syndrome: A Cohort of 24 Patients (ALAZA-24)

Objectif(s) de la recherche et intérêt pour la santé publique

Finalité de l'étude

Objectifs poursuivis

Domaines médicaux investigués

Bénéfices attendus

Introduction

Alazami syndrome (AS, MIM 615071) is a rare autosomal recessive disorder caused by pathogenic variants in the LARP7 gene, a key regulator of RNA polymerase II transcription via the 7SK snRNP complex. Approximately 50 patients have been reported to date. The phenotype includes severe intellectual disability, short stature, microcephaly, skeletal dysplasia, and multisystem involvement.

Recent studies suggest a potential role of LARP7 in telomere biology through its interaction with telomerase RNA processing. However, this association remains insufficiently explored.

This study aims to expand the phenotypic, radiographic, and molecular spectrum of AS and explore a potential correlation with telomere length.

Hypothesis:
The phenotypic spectrum of AS is broader than currently described.
Certain variants (including a potential founder mutation in La Réunion) may correlate with specific clinical patterns.
LARP7 dysfunction may influence telomere homeostasis.

Description of the clinical spectrum: the full range of clinical manifestations; indeed, clinical manifestations vary widely among patients with the same genetic disorder, as some may have malformations that others do not, or may have more severe neurodevelopmental impairment than others.

Objectif principal
Décrire le spectre clinique, radiologique et génétique d’une cohorte française de 24 patients atteints du syndrome d’Alazami.

Objectif(s) secondaire(s)
- Identifier d’éventuelles corrélations génotype-phénotype
- Décrire de nouvelles anomalies phénotypiques, notamment squelettiques
-Étudier la longueur des télomères chez un sous-groupe de patients (ce sont les patients ayant déjà eu cette analyse dans le cadre de leur prise en charge)
- Comparer les données de la cohorte à celles de la littérature