MYT1 role in the microtia-craniofacial microsomia spectrum

Q2Background: Craniofacial microsomia (CFM), also known as the oculo-auriculovertebral spectrum, comprises a variable phenotype with the most common features including microtia and mandibular hypoplasia on one or both sides, in addition to lateral oral clefts, epibulbar dermoids, cardiac, vertebral, and renal abnormalities. The etiology of CFM is largely unknown. The MYT1 gene has been reported as a candidate based in mutations found in three unrelated individuals. Additional patients with mutations in this gene are required to establish its causality. We present two individuals with CFM that have rare variants in MYT1 contributing to better understand the genotype and phenotype associated with mutations in this gene. Methods/Results: We conducted genetic analysis using whole-exome and -genome sequencing in 128 trios with CFM. Two novel MYT1 mutations were identified in two participants. Sanger sequencing was used to confirm these mutations. Conclusion: We identified two additional individuals with CFM who carry rare variants in MYT1, further supporting the presumptive role of this gene in the CFM spectrum.N/

Damaging variants in FOXI3 cause microtia and craniofacial microsomia

Q1Q1Pacientes con Microtia y Microsomía craneofacialPurpose: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. Methods: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. Results: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. Conclusion: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.https://orcid.org/0000-0003-3822-7780https://orcid.org/0000-0002-0729-6866Revista Internacional - IndexadaA1N

Haploinsufficiency of SF3B2 causes craniofacial microsomia

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 highlyQ1Revista Internacional - IndexadaA1S