Open AccessA novel CEP57 variant associated with mosaic variegated aneuploidy syndrome in a Chinese female presenting with short stature, microcephaly, brachydactyly, and small teeth
Author(s) -
Feng Biyun,
Chang Guoying,
Zhang Qianwen,
Li Xin,
Tang Yijun,
Gu Shili,
Wang Yirou,
Wang Jian,
Wang Xiumin
Publication year - 2022
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1951
Subject(s) - microcephaly , short stature , brachydactyly , sanger sequencing , exome sequencing , genetics , karyotype , exome , medicine , biology , pediatrics , mutation , chromosome , gene
Background Mosaic variegated aneuploidy (MVA) syndrome is a rare, autosomal recessive genetic disease. Here, we report an ultra‐rare case of MVA syndrome associated with a CEP57 variant. Methods We retrospectively analyzed the clinical data of a 9‐year‐old female patient and surveyed her family members. Whole‐exome sequencing and karyotype analysis were performed; suspected mutations were verified using Sanger sequencing. Results The patient presented with intrauterine growth restriction, short stature, microcephaly, facial dysmorphism, brachydactyly, and small teeth, and she showed unsatisfactory response to GH replacement therapy. Laboratory tests revealed high insulin‐like growth factor‐1 levels. Karyotype analysis of the peripheral blood showed mosaic variegated aneuploidies. Whole‐exome and Sanger sequencing revealed a novel homozygous nonsense variant, NM_014679.4: c.312 T > G, in CEP57 that leads to translation termination (p.Tyr104*). The parents were heterozygous carriers of the identified variant. Conclusion This study presents an ultra‐rare case of CEP57‐ driven MVA syndrome, identifying a novel homozygous nonsense variant of CEP57 (p.Tyr104*). Our findings enrich the CEP57 mutational spectrum and emphasize the importance of genetic testing in patients with microcephaly and short stature. Furthermore, we conclude that growth hormone treatment is ineffective in such patients.