FLNB In Skeletal Disease
2. FLNB in Skeletal Diseases
Mutations in FLNB lead to various skeletal malformations, involving long bone, joints and vertebra. There were five FLNB-related skeletal disorders been reported so far, including spondylocarpotarsal synostosis (SCT), Larsen syndrome, atelosteogenesis (AO), boomerang dysplasia, and isolated congenital talipes equinovarus.
(1) Spondylocarpotarsal synostosis syndrome (SCT, OMIM 272460)
Spondylocarpotarsal synostosis syndrome was characterized by the following features: fused vertebrae malformation including scoliosis and lordosis, and fused carpal and tarsal joints. Two brothers with recessively inherited scoliosis with unilateral unsegmented bar were first reported by Langer et al. in 1975 (Langer and Moe, …show more content…
Bicknell et al. studied 20 probands with Larsen syndrome and their pedigrees (Bicknell et al., 2007), and found that despite those inter-familial and intra-familial variation in phenotypes of Larsen syndrome, supernumerary ossification centers of carpal or tarsal were invariant characteristics in all patients with Larsen syndrome (Figure 2A). This phenomenon was quite the opposite in SCT patients, who presented with premature fusion of carpal and tarsal bones (Figure 2B). Missense mutations and small in-frame deletions within FLNB are the causative mutations for Larsen syndrome, while only nonsense mutations in FLNB have been reported in SCT (Sawyer et al., 2009). Therefore, we suggested that SCT was caused by a complete loss of function of FLNB led by nonsense mutations on this gene. Daniel et al. proposed that missense mutations on acting-binding domain (ABD) led to increase of actin-filamin compound in cytoplasm, the amount of which was correlated with phenotype severity of Larsen syndrome (Daniel et al., 2012). And Sawyer et al. found that missense mutations in ABD could increase the affinity between FLNB and actin. These findings might explain difference between phenotypes of Larsen syndrome and those of SCT. The contradictions in phenotypes between SCT and Larsen syndrome indicates the important role of FLNB in the formation of bone ossification
Mutations in FLNB lead to various skeletal malformations, involving long bone, joints and vertebra. There were five FLNB-related skeletal disorders been reported so far, including spondylocarpotarsal synostosis (SCT), Larsen syndrome, atelosteogenesis (AO), boomerang dysplasia, and isolated congenital talipes equinovarus.
(1) Spondylocarpotarsal synostosis syndrome (SCT, OMIM 272460)
Spondylocarpotarsal synostosis syndrome was characterized by the following features: fused vertebrae malformation including scoliosis and lordosis, and fused carpal and tarsal joints. Two brothers with recessively inherited scoliosis with unilateral unsegmented bar were first reported by Langer et al. in 1975 (Langer and Moe, …show more content…
Bicknell et al. studied 20 probands with Larsen syndrome and their pedigrees (Bicknell et al., 2007), and found that despite those inter-familial and intra-familial variation in phenotypes of Larsen syndrome, supernumerary ossification centers of carpal or tarsal were invariant characteristics in all patients with Larsen syndrome (Figure 2A). This phenomenon was quite the opposite in SCT patients, who presented with premature fusion of carpal and tarsal bones (Figure 2B). Missense mutations and small in-frame deletions within FLNB are the causative mutations for Larsen syndrome, while only nonsense mutations in FLNB have been reported in SCT (Sawyer et al., 2009). Therefore, we suggested that SCT was caused by a complete loss of function of FLNB led by nonsense mutations on this gene. Daniel et al. proposed that missense mutations on acting-binding domain (ABD) led to increase of actin-filamin compound in cytoplasm, the amount of which was correlated with phenotype severity of Larsen syndrome (Daniel et al., 2012). And Sawyer et al. found that missense mutations in ABD could increase the affinity between FLNB and actin. These findings might explain difference between phenotypes of Larsen syndrome and those of SCT. The contradictions in phenotypes between SCT and Larsen syndrome indicates the important role of FLNB in the formation of bone ossification