Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts

Huang, Wenbin; Zhang, Shiying; Jun, Lin; Ding, Yi; Jiang, Nan; Zhang, Jieni; Zhao, Huaxiang; Chen, Feng

doi:10.1016/j.jgg.2023.03.012

Cited by 5 publications

(2 citation statements)

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“…GOF may exert their effect through various mechanisms such as constitutive or ectopic activation, shift of substrate or binding target specificity, or protein aggregation [ 11 ]. Recently, Huang et al reported two heterozygous variants (c.1321C>CA and c.1693C>A) in two different families with nonsyndromic clefts of lip/palate [ 12 ]. The authors argued that the variants resulted in loss-of-function.…”

Section: Discussionmentioning

confidence: 99%

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A Stop-gain Variant c.220C>T (p.(Gln74*)) in FLNB Segregates with Spondylocarpotarsal Synostosis Syndrome in a Consanguineous Family

Shahid,

Shakoor,

Bibi

et al. 2023

Yale J Biol Med

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Spondylocarpotarsal synostosis (SCT) syndrome is a very rare and severe form of skeletal dysplasia. The hallmark features of SCT are disproportionate short stature, scoliosis, fusion of carpal and tarsal bones, and clubfoot. Other common manifestations are cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Homozygous variants in FLNB are known to cause SCT. This study was aimed to investigate the phenotypic and genetic basis of unique presentation of SCT syndrome segregating in a consanguineous Pakistani family. Three of the four affected siblings evaluated had severe short stature, short trunk, short neck, kyphoscoliosis, pectus carinatum, and winged scapula. The subjects had difficulty in walking and gait problems and complained of knee pain and backache. Roentgenographic examination of the eldest patient revealed gross anomalies in the axial skeleton including thoracolumbar and cervical fusion of ribs, severe kyphoscoliosis, thoracic and lumbar lordosis, coxa valga, fusion of certain carpals and tarsals, and clinodactyly. The patients had normal faces and lacked other typical features of SCT like cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Whole exome sequencing (WES) of two affected siblings led to the discovery of a rare stop-gain variant c.220C>T (p.(Gln74*)) in exon 1 of the FLNB gene. The variant was homozygous and segregated with the malformation in this family. This study reports extensive phenotypic variability in SCT and expands the mutation spectrum of FLNB .

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Section: Discussionmentioning

confidence: 99%

“…Further, Klippel-Feil syndrome 1 which segregates autosomal dominantly, generally does not show carpal or tarsal fusions, instead, there are isolated cervical fusions which do not occur in SCT syndrome. Another vertebral malformation, [12]. The authors argued that the variants resulted in loss-of-function.…”

Section: Discussionmentioning

confidence: 99%