Biomaterial Database

Homozygous loss-of-function variants in FILIP1 cause autosomal recessive arthrogryposis multiplex congenita with microcephaly. 2023

Franziska Schnabel, and Elisabeth Schuler, and Almundher Al-Maawali, and Ankur Chaurasia, and Steffen Syrbe, and Adila Al-Kindi, and Gandham SriLakshmi Bhavani, and Anju Shukla, and Janine Altmüller, and Peter Nürnberg, and Siddharth Banka, and Katta M Girisha, and Yun Li, and Bernd Wollnik, and Gökhan Yigit

Institute of Human Genetics, University Medical Center Göttingen, Heinrich-Düker-Weg 12, 37073, Göttingen, Germany.

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 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.

UI	MeSH Term	Description	Entries
D008831	Microcephaly	A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)	Microlissencephaly,Severe Congenital Microcephaly,Congenital Microcephalies, Severe,Congenital Microcephaly, Severe,Microcephalies,Microcephalies, Severe Congenital,Microcephaly, Severe Congenital,Microlissencephalies,Severe Congenital Microcephalies
D010375	Pedigree	The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.	Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D003286	Contracture	Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint.	Contractures
D003598	Cytoskeletal Proteins	Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.	Proteins, Cytoskeletal
D006720	Homozygote	An individual in which both alleles at a given locus are identical.	Homozygotes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001176	Arthrogryposis	Persistent flexure or contracture of a joint.	Amyoplasia Congenita,Arthromyodysplasia, Congenital,Guerin-Stern Syndrome,Myodystrophia Fetalis Deformans,Arthrogryposis Multiplex Congenita,Arthrogryposis Multiplex Congenita (AMC),Congenital Arthromyodysplasia,Congenital Multiple Arthrogryposis,Fibrous Ankylosis of Multiple Joints,Guérin-Stern Syndrome,Otto Syndrome,Rocher-Sheldon Syndrome,Rossi Syndrome,Arthrogryposes,Arthrogryposes, Congenital Multiple,Arthrogryposis Multiplex Congenitas,Arthrogryposis Multiplex Congenitas (AMC),Arthrogryposis, Congenital Multiple,Arthromyodysplasias, Congenital,Congenita, Arthrogryposis Multiplex,Congenita, Arthrogryposis Multiplex (AMC),Congenital Arthromyodysplasias,Congenital Multiple Arthrogryposes,Congenitas, Arthrogryposis Multiplex,Congenitas, Arthrogryposis Multiplex (AMC),Guerin Stern Syndrome,Guérin Stern Syndrome,Multiple Arthrogryposes, Congenital,Multiple Arthrogryposis, Congenital,Multiplex Congenita, Arthrogryposis,Multiplex Congenita, Arthrogryposis (AMC),Multiplex Congenitas, Arthrogryposis,Multiplex Congenitas, Arthrogryposis (AMC),Rocher Sheldon Syndrome,Syndrome, Guerin-Stern,Syndrome, Guérin-Stern,Syndrome, Otto,Syndrome, Rocher-Sheldon,Syndrome, Rossi