Dataset Information

Haploinsufficiency of SF3B2 causes craniofacial microsomia.

ABSTRACT: Craniofacial microsomia (CFM) is the second most common congenital facial anomaly, yet its genetic etiology remains unknown. We perform whole-exome or genome sequencing of 146 kindreds with sporadic (n = 138) or familial (n = 8) CFM, identifying a highly significant burden of loss of function variants in SF3B2 (P = 3.8 × 10^-10), a component of the U2 small nuclear ribonucleoprotein complex, in probands. We describe twenty individuals from seven kindreds harboring de novo or transmitted haploinsufficient variants in SF3B2. Probands display mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities. Targeted morpholino knockdown of SF3B2 in Xenopus results in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease. The results establish haploinsufficient variants in SF3B2 as the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases.

SUBMITTER: Timberlake AT

PROVIDER: S-EPMC8333351 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Haploinsufficiency of SF3B2 causes craniofacial microsomia.

Timberlake Andrew T AT Griffin Casey C Heike Carrie L CL Hing Anne V AV Cunningham Michael L ML Chitayat David D Davis Mark R MR Doust Soghra J SJ Drake Amelia F AF Duenas-Roque Milagros M MM Goldblatt Jack J Gustafson Jonas A JA Hurtado-Villa Paula P Johns Alexis A Karp Natalya N Laing Nigel G NG Magee Leanne L Mullegama Sureni V SV Pachajoa Harry H Porras-Hurtado Gloria L GL Schnur Rhonda E RE Slee Jennie J Singer Steven L SL Staffenberg David A DA Timms Andrew E AE Wise Cheryl A CA Zarante Ignacio I Saint-Jeannet Jean-Pierre JP Luquetti Daniela V DV

Nature communications 20210803 1

Craniofacial microsomia (CFM) is the second most common congenital facial anomaly, yet its genetic etiology remains unknown. We perform whole-exome or genome sequencing of 146 kindreds with sporadic (n = 138) or familial (n = 8) CFM, identifying a highly significant burden of loss of function variants in SF3B2 (P = 3.8 × 10<sup>-10</sup>), a component of the U2 small nuclear ribonucleoprotein complex, in probands. We describe twenty individuals from seven kindreds harboring de novo or transmitte ...[more]

PMID: 34344887

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Project description:IntroductionAsymmetric mandibular hypoplasia, microtia, tongue and laryngeal anomalies, and soft palate and facial nerve dysfunction are clinical features observed in children with craniofacial microsomia (CFM). Despite involvement of all these structures in hearing and speech, there is limited evidence reporting speech outcomes in this population. Systematic reviews of clinical and surgical interventions related to CFM have been published, but no methodological review of speech outcomes exists. This scoping review will summarise what is known about speech production in individuals with CFM as well as illustrate gaps in the existing body of literature that will guide future research.Methods/analysisThis review will follow the methodological framework for scoping reviews first reported by Arksey & O'Malley and revised by Levac and others. Databases searched will include Ovid MEDLINE, EMBASE, CINAHL, PsycINFO and grey literature. Articles reporting any parameter of speech production in individuals with CFM will be considered for inclusion. Articles published in a language other than English will be excluded. Articles will be screened in three stages: (1) title review, (2) abstract review and (3) full text review. Ten per cent of articles will be rescreened by a second reviewer. Reference lists will be hand reviewed to identify additional relevant articles. Data charting will capture article metadata, study population and design, CFM diagnostic criteria, speech outcome measurement and key findings. The Preferred Reporting Systems for Systematic Reviews and Meta-Analyses Protocols-Extension for Scoping Reviews checklist will guide reporting of results. Descriptive analysis and data visualisation strategies will be used.Ethics and disseminationInstitutional review board approval is not required for a scoping review, as it does not directly involve human subjects. Results will be disseminated through peer-reviewed publication as well as conference presentation.

Dataset Information

Haploinsufficiency of SF3B2 causes craniofacial microsomia.

Publications

Haploinsufficiency of SF3B2 causes craniofacial microsomia.

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