FLNA Variants Related to Melnick-Needles Syndrome: Two Mexican Case Reports and a Comprehensive Variant Review

Area of Science:

• Genetics
• Molecular Biology
• Skeletal Dysplasias

Background:

• Melnick-Needles Syndrome (MNS) is a severe X-linked dominant osteochondrodysplasia.
• It results from gain-of-function variants in the FLNA gene, encoding the cytoskeletal protein Filamin A.
• MNS presents with short stature, facial dysmorphism, skeletal anomalies, and systemic complications.

Purpose of the Study:

• To investigate the genetic and phenotypic spectrum of Melnick-Needles Syndrome.
• To describe two novel Mexican cases of MNS with distinct FLNA missense variants.
• To review existing literature on FLNA variants associated with MNS.

Main Methods:

• Case presentation of two Mexican patients diagnosed with MNS.
• Identification of FLNA missense variants p.(Leu1193Pro) and p.(Ser1199Leu).
• Comprehensive literature review of FLNA variants in MNS.

Main Results:

• Two distinct FLNA missense variants, p.(Leu1193Pro) and p.(Ser1199Leu), were identified in the Mexican cases.
• The study reinforces the significant genetic and phenotypic variability of MNS.
• Exon 22 variants in FLNA are critically implicated in MNS pathogenesis.

Conclusions:

• FLNA variants contribute to a wide spectrum of disorders, with MNS being a severe phenotype.
• Understanding the FLNA genetic and phenotypic spectrum is crucial for MNS diagnosis and management.
• Exon 22 variants play a pivotal role in the development of Melnick-Needles Syndrome.