Identification of a De Novo Heterozygous Frameshift Variant in FMR1 in a Female With Fragile X Syndrome.

We present a 28-year-old Spanish female with a de novo heterozygous variant in FMR1 (NM_002024.6:c.1061_1062delAA), p.(Lys354Thrfs*15) detected by whole-exome sequencing and confirmed by Sanger sequencing from cDNA. She was born full-term with neonatal jaundice requiring phototherapy. At age 11, she exhibited weight and head circumference > 97th percentile, global developmental delay, mild ID (IQ: 71), and hyperactivity. FMR1 CGG analysis was normal. NGS panel of over 200 OGS-related genes found no pathogenic variants. By age 28, she presented with macrocephaly, coarse facial features, mild joint hypermobility, left talo-valgus, a port-wine stain, a café-au-lait spot, and a piezogenic papule. Herein, we describe a clinical and molecular report of the second FXS female patient due to a heterozygous point variant. This study was approved by the ethical committee of Hospital Universitario La Paz (CEIm PI-446), and informed consent was obtained from the patient and her parents.