46,Xy Dsdand Limb Abnormalities In A Female With A De Novolhx9missense Mutation

Differences in sex development (DSD) are a group of rare conditions involving genes, hormones and reproductive organs, including genitals. Although these disorders are common, information about the molecular causes remain limited. Many genes have been identified in association with DSD but in many cases the causative gene could not be identified. TheLhx9gene has been studied in mice and birds, and biallelic mutations in this gene have been found to cause 46,XY DSD and limb abnormalities. So far two variants ofLHX9have been identified in 46,XY individuals with testicular regression, micropenis and hypospadias. We report a de novo heterozygous missense variant inLHX9in a girl with 46,XY DSD and finger and toe abnormalities. It was previously predicted that a mutation inLHX9would not cause extragenital anomalies in light of prior animal studies, but our report adds to the limited knowledge of the phenotype observed in humans with a variant inLHX9. To the best of our knowledge this is the first reported case with this combination of abnormalities.