Homozygous loss-of-function variants in FILIP1 cause autosomal recessive arthrogryposis multiplex congenita with microcephaly
Exome sequencing
Carrier Proteins/genetics
Contracture
Epidemiology
Physiology
Mechanosensitive Ion Channels in Physiology and Disease
Arthrogryposis/genetics
Cytoskeletal Proteins/genetics
Arthrogryposis multiplex congenita
Gene
Microcephaly/genetics
Role of Autophagy in Disease and Health
Health Sciences
Genetics
Humans
Biology
Original Investigation
Arthrogryposis
Homozygote
Pedigree
3. Good health
Cytoskeletal Proteins
Phenotype
FOS: Biological sciences
Spinal Muscular Atrophy
Microcephaly
Medicine
Gene Therapy for Spinal Muscular Atrophy
Technology Platforms
Genes, Cells and Cell-Based Medicine [Topic 1]
Carrier Proteins
DOI:
10.1007/s00439-023-02528-2
Publication Date:
2023-03-21T11:02:51Z
AUTHORS (15)
ABSTRACT
AbstractArthrogryposis multiplex congenita forms a broad group of clinically and etiologically heterogeneous disorders characterized by congenital joint contractures that involve at least two different parts of the body. Neurological and muscular disorders are commonly underlying arthrogryposis. Here, we report five affected individuals from three independent families sharing an overlapping phenotype with congenital contractures affecting shoulder, elbow, hand, hip, knee and foot as well as scoliosis, reduced palmar and plantar skin folds, microcephaly and facial dysmorphism. Using exome sequencing, we identified homozygous truncating variants in FILIP1 in all patients. FILIP1 is a regulator of filamin homeostasis required for the initiation of cortical cell migration in the developing neocortex and essential for the differentiation process of cross-striated muscle cells during myogenesis. In summary, our data indicate that bi-allelic truncating variants in FILIP1 are causative of a novel autosomal recessive disorder and expand the spectrum of genetic factors causative of arthrogryposis multiplex congenita.
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REFERENCES (30)
CITATIONS (1)
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