Homozygous loss-of-function variants in FILIP1 cause autosomal recessive arthrogryposis multiplex congenita with microcephaly

• DOI: 10.1007/s00439-023-02528-2
• Publication Date: 2023-03-21T11:02:51Z
• Authors: Franziska Schnabel; Elisabeth Schuler; Almundher Al-Maawali; Ankur Chaurasia; Steffen Syrbe; Adila Al-Kindi; Gandham SriLakshm...; Anju Shukla; Janine Altmüller; Peter Nürnberg; Siddharth Banka; Katta M. Girisha; Yun Li; Bernd Wollnik; Gökhan Yigit
• Keywords: Arthrogryposis multiplex congenita; Microcephaly

Arthrogryposis multiplex congenita forms a broad group of clinically and etiologically heterogeneous disorders characterized by congenital joint contractures that involve at least two different parts the body. Neurological muscular are commonly underlying arthrogryposis. Here, we report five affected individuals from three independent families sharing an overlapping phenotype with affecting shoulder, elbow, hand, hip, knee foot as well scoliosis, reduced palmar plantar skin folds, microcephaly facial dysmorphism. Using exome sequencing, identified homozygous truncating variants in FILIP1 all patients. is regulator filamin homeostasis required for initiation cortical cell migration developing neocortex essential differentiation process cross-striated muscle cells during myogenesis. In summary, our data indicate bi-allelic causative novel autosomal recessive disorder expand spectrum genetic factors arthrogryposis congenita.