Novel Compound Heterozygous Variants in the CDC6 Gene in a Russian Patient with Meier-Gorlin Syndrome

BACKGROUND: Meier-Gorlin syndrome (MGS) is a rare genetic syndrome inherited in an autosomal dominant or autosomal recessive manner. The disorder is characterized by bilateral microtia, absence or hypoplasia of the patella, and an intrauterine growth retardation as well as a number of other characteristic features. The cause of the disease is mutations in genes encoding proteins involved in the regulation of the cell cycle (ORC1, ORC4, ORC6, CDT1, CDC6, GMNN, CDC45L, MCM3, MCM5, MCM7, GINS2, and DONSON). Meier-Gorlin syndrome 5 due to mutations in the CDC6 gene is difficult to diagnose, and few clinical data have been described to date. Only one patient (male) with a missense mutation in a homozygous state has been previously reported. This report describes a new clinical case of Meier-Gorlin syndrome 5. This is also the first report of a Russian patient with Meier-Gorlin syndrome. CASE PRESENTATION: The patient, a female, had extremely low physical development, neonatal progeroid appearance, lipodystrophy, thin skin, partial alopecia, cyanosis of the face, triangular face, microgenia, arachnodactyly, delayed bone age, hepatomegaly, hypoplasia of the labia majora, and hypertrophy of the clitoris in addition to known clinical signs. Differential diagnosis was performed with chromosomal abnormalities and Hutchinson-Gilford progeria. According to the results of sequencing of the clinical exome, the patient had two previously undescribed variants in the CDC6 gene, c.230A>G (p.(Lys77Arg)) and c.232C>T (p.(Gln78Ter)), NM_001254.3, in a compound heterozygous state. CONCLUSION: This case allows us to learn more about the clinical features and nature of MGS 5 and improve the speed of diagnostics and quality of genetic counseling for such families.