A case report of Indian siblings with short stature due to novel variant in the CEP57 gene, causing Mosaic Variegated Aneuploidy Syndrome Type 2 and review of the phenotype of related patients

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2024年9月18日

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Smita Mundada,
Suvarna Magar,
Pooja Kalai,
Prabha More Khaire

摘要

Introduction

Mosaic Variegated Aneuploidy Syndrome 2 (MVA2) is a rare genetic disorder characterized by a variable percentage (25–50%) of constitutional mosaic aneuploidies. To our knowledge, only 15 cases worldwide with only 1 Indian family and six pathogenic variants of MVA2 have been described.

Clinical features

We now report a 2nd Indian family with two female siblings who presented with short stature, dysmorphism, microcephaly, and a history of consanguinity.

Diagnosis and intervention

Karyotyping was reported to be normal (46, XX) in both siblings. Whole exome and Sanger sequencing revealed a homozygous c.1388_1391del(p.Lys463IlefsTer3) in exon 11 in the CEP57 gene (NM_014679.5), a novel variant that leads to the termination of protein translation causing MVA2. Testing of a phenotypically typical sibling showed a heterozygous status for the identified variant.

Conclusion

This report highlights an important lesson for genetic testing. Our findings enrich the CEP57 mutational spectrum and emphasize the importance of genetic testing and karyotyping in patients with microcephaly and short stature.