Identification of a Chinese patient with MTSS2-causing intellectual disability by WES reanalysis

Intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF) is an extremely rare disease caused by a heterozygous pathogenic variant in the MTSS2 gene with an autosomal dominant inheritance pattern. To date, only 10 patients with IDDOF and one pathogenic variant in the MTSS2 gene have been reported. Here, we present a new Chinese patient with IDDOF, who is the 11th patient worldwide and the second case in China. The proband presented with relative microcephaly, distinctive facial features of bitemporal narrowing and ptosis, ophthalmological and auditory findings, hypotonia, psychomotor developmental delay, intellectual disability, and emotional and behavioral problems. Whole exome sequencing (WES) initially did not find a phenotype-contributing variant in 2021, whereas reanalysis of WES data in 2024 revealed that the de novo c.2011C>T(p.Arg671Trp) heterozygous variant of the MTSS2 gene in the patient turned out to be pathogenic, which had been reported to cause IDDOF in 2022. Our study reports an additional patient and new phenotypes for IDDOF and suggests the c.2011C>T(p.Arg671Trp) variant in the MTSS2 gene as a hotspot. Our work shares our diagnostic experience and indicates the potential of WES reanalysis in negative cases to improve diagnostic yield, particularly in rediscovering previously unknown gene-disease associations

Disease · Exome sequencing · Identification (biology · Intellectual disability · Proband · Psychomotor learning · Psychomotor retardation · Rare disease · Genomic variations and chromosomal abnormalities · Genomics and Rare Diseases · Ocular Disorders and Treatments