Identification of a de novo PUF60 variant associated with craniofacial microsomia.

American journal of medical genetics. Part A 2024 Sep

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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. © 2024 Wiley Periodicals LLC.

Citation

Takuya Ogawa, Jingyi Xue, Long Guo, Maristela Sayuri Inoue-Arai, Siulan Vendramini-Pittoli, Roseli Maria Zechi-Ceide, Rosana Maria Candido-Souza, Cristiano Tonello, Michele Madeira Brandão, Terumi Okada Ozawa, Adriano Porto Peixoto, Daniela Maria Cury Ferreira Ruiz, Tomoki Nakashima, Shiro Ikegawa, Keiji Moriyama, Nancy Mizue Kokitsu-Nakata. Identification of a de novo PUF60 variant associated with craniofacial microsomia. American journal of medical genetics. Part A. 2024 Sep;194(9):e63631