<unk>  is caused by heterozygous mutations in the SON gene. As an autosomal dominant disease, children with parents carrying a SON mutation have a 50% risk of inheriting the mutation. However, the majority of affected individuals have de novo mutations in the SON gene and<unk>  is not inherited to their children. Allelic Variants of SON Gene Many individuals with<unk>  have identified heterozygosity for a de novo 4-base pair deletion, de novo mutation in exon 3 in the SON gene and de novo 2-base point insertion in exon, resulting in haploinsufficiency or a frameshift and premature termination in the arginine/serine (RS) domain. Peripheral blood cells from the sampled patients confirmed decreased levels of the mutant RNA transcript, consistent with haploinsufficiency. Other mutations observed include a nonsense mutation, an in-frame deletion of amino acids and an entire gene deletion. De novo heterozygous 1-base point duplication in exon 3 and 1-base point deletion in exon 4 of the SON gene resulted in a frameshift and premature termination. Parental DNA has confirmed that de novo mutations are common in patients with<unk> . De novo LoF mutations and haploinsufficiency for the SON gene are shown to cause profound developmental malformations during embryonic development as seen in the phenotypic manifestations of the<unk> . Structure of SON Gene SON is a large protein consisting of 2426 amino acids and repeat sequences. SON is located within the human chromosomal region 21q22.11 in nuclear speckles and consists of 12 exons. Exon 3 of the SON gene is particularly large, accounting for 82% of the entire coding region. The majority of SON variants found in<unk>  individuals are localised to exon 3.
ZTTK syndrome
ATR-16 syndrome
CAMFAK syndrome
ATR-X syndrome
Treacher Collins syndrome
MEDNIK syndrome
GRACILE syndrome
LIG4 syndrome