Identification of a de novo PUF60 variant associated with craniofacial microsomia
Takuya Ogawa1, Jingyi Xue2,3, Long Guo2,4
1Department of Maxillofacial Orthognathics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Abstract:
Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities. A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in PUF60 was identified, which was predicted to be pathogenic in silico. PUF60 has been reported as a causal gene in Verheij syndrome, but not in CFM. Although the boy showed craniofacial abnormalities and developmental delay that overlapped with Verheij syndrome, the facial asymmetry with unilateral hypoplasia of the mandible observed in this case did not match the previously reported phenotypes of PUF60 variants. Our findings expand the phenotypic range of PUF60 variants that cover CFM and Verheij syndrome.
Insights
A genetic variant in PUF60 was identified in a Brazilian family with craniofacial microsomia (CFM). This finding expands the known spectrum of PUF60-related disorders, linking it to CFM.
Area of Science:
- Genetics
- Developmental Biology
- Medical Science
Background:
- Craniofacial microsomia (CFM), or oculo-auriculo-vertebral spectrum, is a congenital disorder affecting first and second branchial arch derivatives.
- Distinguishing CFM from other branchial arch syndromes is challenging, with genetic causes often unidentified.
Observation:
- Exome sequencing was performed on a Brazilian family presenting with CFM.
- The proband, a 12-month-old boy, exhibited unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities.
Findings:
- A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in the PUF60 gene was identified in the proband.
- This variant, predicted pathogenic in silico, has previously been associated with Verheij syndrome but not CFM.
Implications:
- The study expands the phenotypic spectrum of PUF60 variants to include craniofacial microsomia.
- This discovery aids in diagnosing CFM and understanding the genetic basis of branchial arch abnormalities.
