@article {205,
	title = {Biallelic truncating mutations in FMN2, encoding the actin-regulatory protein Formin 2, cause nonsyndromic autosomal-recessive intellectual disability.},
	journal = {Am J Hum Genet},
	volume = {95},
	year = {2014},
	month = {2014 Dec 04},
	pages = {721-8},
	abstract = {<p>Dendritic spines represent the major site of neuronal activity in the brain; they serve as the receiving point for neurotransmitters and undergo rapid activity-dependent morphological changes that correlate with learning and memory. Using a combination of homozygosity mapping and next-generation sequencing in two consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability, we identified truncating mutations in formin 2 (FMN2), encoding a protein that belongs to the formin family of actin cytoskeleton nucleation factors and is highly expressed in the maturing brain. We found that FMN2 localizes to punctae along dendrites and that germline inactivation of mouse Fmn2 resulted in animals with decreased spine density; such mice were previously demonstrated to have a conditioned fear-learning defect. Furthermore, patient neural cells derived from induced pluripotent stem cells showed correlated decreased synaptic density. Thus, FMN2 mutations link intellectual disability either directly or indirectly to the regulation of actin-mediated synaptic spine density. </p>},
	keywords = {Adolescent, Adult, Base Sequence, Chromosome Disorders, Cohort Studies, Consanguinity, Egypt, Exome, Female, Genes, Recessive, Genetic Linkage, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Intellectual Disability, Male, Microfilament Proteins, Molecular Sequence Data, Nuclear Proteins, Pakistan, Pedigree, Sequence Analysis, DNA, Sequence Deletion},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2014.10.016},
	author = {Law, Rosalind and Dixon-Salazar, Tracy and Jerber, Julie and Cai, Na and Abbasi, Ansar A and Zaki, Maha S and Mittal, Kirti and Gabriel, Stacey B and Rafiq, Muhammad Arshad and Khan, Valeed and Nguyen, Maria and Ali, Ghazanfar and Copeland, Brett and Scott, Eric and Vasli, Nasim and Mikhailov, Anna and Khan, Muhammad Nasim and Andrade, Danielle M and Ayaz, Muhammad and Ansar, Muhammad and Ayub, Muhammad and Vincent, John B and Gleeson, Joseph G}
}
