A patient with mosaic USP9X gene variant

Area of Science:

• Genetics
• Developmental Biology
• Medical Genetics

Background:

• Female-restricted X-linked mental retardation (MRXS99F) is a rare syndrome linked to USP9X gene variants.
• It is characterized by developmental delay and specific congenital anomalies.

Observation:

• A female fetus presented with MRXS99F due to a novel USP9X frameshift variant (c.6679_6685delAAATTATinsTCCTG).
• The variant showed mosaicism in amniocytes and peripheral blood.
• Prenatal findings included enlarged posterior cranial fossa, cerebellar abnormalities, corpus callosum agenesis, cardiac defect, and single umbilical artery.

Findings:

• Postnatal observations revealed anal anteriorization, choanal atresia, olfactory bulb hypoplasia, widened subarachnoid spaces, and delayed myelination.
• By 18 months, severe growth and global developmental delay, moderate deafness, dental enamel erosions, and scoliosis were noted.
• X-inactivation analysis showed partial skewing with 80% inactive paternal X.

Implications:

• This study reports comprehensive prenatal and postnatal features of MRXS99F associated with a mosaic USP9X variant.
• It contributes to understanding genotype-phenotype correlations in MRXS99F.
• The findings emphasize the importance of genetic analysis in diagnosing complex developmental disorders.