Title : A SOX3 (Xq27.1- Xq27.3) duplication in a boy with neuro developmental delays, autism spectrum disorders and macrocephaly
Background:Chromosomal rearrangements (duplication/deletion) were described as a cause of neurodevelopmental diseases in 7 – 10 % of cases. The impact of these changes mainly depends on overlapped genes. SRY-Box Transcription Factor 3 (SOX3, *313430) is located on the long arm of the X chromosome. Aberrations of this gene were associated with X-linked Mental retardation with isolated growth hormone deficiency (MR-GHD, OMIM: 300123). Nevertheless, only a few cases have as yet been extensively described.
Design: A 3-year 9 month-old male was indicated to genetics testing for neurodevelopmental delays (ND), autism spectrum disorders (ASD), and macrocephaly. The patient was born at term after labor induction as a second child of nonconsanguineous parents; the mother and father were 26 years old. Birth rates were 3650 g and 51 cm (both 50th percentile). ND and macrocephaly had been noted since birth. ASD was diagnosed by psychiatrists in his 3 years old. The head circumstance was 54 cm (100th percentile), high 97 cm (50th percentile), and weight 17 kg (88th percentile) in his 3 years.
Result: The boy had normal karyotype 46, XY and expansion of triplets in promotor of the FMR1 gene (Syndrome fragile X) was excluded. Duplication of Xq27.1-27.3 (Human GRCh38/hg 38 chromosome X: 139532160-144073004, 4.5 Mb) including SOX3 gene was revealed by array comparative genomic hybridization (aCGH). The observed variant was not observed in healthy parents.
Discussions: Product of the SOX3 gene act in cellular processes and functions required for cognitive and pituitary development. Although, deletions of SOX3 were associated with MR-GHD duplication were described as unknown in genetic databases with the milder clinical phenotype (e.g. mild developmental delay, short stature, genital abnormalities). Described cases were mostly boys which lead to the presumption that duplication of Xq27.1-27.3 including SOX3 can arise by de novo or can be inherited from a healthy mother. Additionally, observed duplication induced severe clinical phenotype despite published data.
Conclusion: SOX3 involved in 4.5Mb duplication of X chromosome should be considered for the cause of ND, ASD, and macrocephaly.