ABSTRACT 3 M syndrome (3MS) is a rare autosomal recessive disorder characterized by severe prenatal and postnatal growth retardation, distinctive facial features, and skeletal abnormalities, while cognitive development remains unaffected. This study reports a novel homozygous pathogenic variant in the CUL7 gene identified in an Iranian girl with clinical features consistent with 3MS. Clinical evaluations involved monthly monitoring of the patient's height and weight to assess her growth pattern. Genetic testing, including whole exome sequencing (WES) and Sanger sequencing, was conducted. The identified variant was further analyzed through segregation and bioinformatics analyses. The patient exhibited severe growth retardation in both height and weight, along with a prominent forehead, round eyes, delayed walking, and delayed bone age. WES revealed a pathogenic homozygous variant in the CUL7 gene, c. 4145₄146delinsT p. (Asn1382Ilefs*11), which was confirmed by Sanger sequencing. Segregation analysis demonstrated that both parents and grandmothers were heterozygous carriers of the same mutation, consistent with an autosomal recessive inheritance pattern. The clinical and genetic findings confirmed the diagnosis of 3MS in the patient. This case highlights the pivotal role of molecular diagnostics in confirming rare genetic disorders, especially in populations with high rates of consanguinity. The study expands the genetic spectrum of CUL7 mutations associated with 3MS and underscores the importance of advanced genetic testing in overcoming diagnostic challenges. Further research into the functional consequences of CUL7 mutations may provide valuable insights for developing targeted therapeutic strategies for this rare disorder.
Arefzadeh et al. (Sun,) studied this question.