[Clinical and genetic analysis of three children with Legius syndrome due to variants of SPRED1 gene].

Abstract

Objective: To explore the clinical and genetic characteristics of three children with Leguis syndrome.

Methods: Three children suspected as Legius syndrome at the Henan Children's Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.

Results: All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c.751C>T (p.Arg251Ter194) in child 1, c.229A>T (p.Lys77Ter368) in child 2, and c.1044_1046delinsC (p.R349fs*11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants.

Conclusion: All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.