Potocki–Lupski syndrome

Clinically, PTLS presents as a milder syndrome than SMS, with distinct characteristics, though PTLS can be mistaken for SMS. abnormal social behaviors, learning disabilities, attention-deficit disorder, obsessive-compulsive behaviours, malocclusions, short stature and failure to thrive. After noting that autism is commonly associated with PTLS, researchers at the Centro de Estudios Científicos and the Austral University of Chile genetically engineered a PTLS "model mouse" where the syntenic chromosome segment was duplicated, and examined the social behaviours of these mice versus those without the anomaly (the "wild-type"). One human autism-related symptom is abnormal reciprocal social interaction. The researchers observed that the genetically-engineered mice of both sexes had a slight (statistically insignificant) impairment of their preference of a social target (i.e., a living, breathing mouse) over an inanimate one — the average human will prefer the social target — and preferred to explore newly introduced mice instead of familiar ones, unlike the typical human and mouse preference of a friend over a stranger, demonstrating a change in their liking of social novelty. They also found that male mice, in some scenarios, showed increased anxiety and dominant behaviour than the control group. Anatomically, the engineered mice had a decreased brain-to-body mass ratio and an alteration in the expression of several genes in the hippocampus. == Molecular genetics ==

Both Potocki–Lupski and Smith–Magenis syndromes arise through a faulty non-allelic homologous recombination mechanism. Both appear to involve a 1.3-3.7Mb chromosome section in 17p11.2 that includes the retinoic acid inducible 1 (RAI1) gene. This conserved sequence has been exploited to learn more about SMS and PTLS. Through genetic studies on both laboratory mice and humans, it has been discovered that RAI1 is likely the gene responsible for these syndromes. For example, in one study, it was shown that mice with 2 copies of the RAI1 gene and 3 copies of each of the other 18 genes in the described translocated region of chromosome 11 appeared and behaved like the control mice with the described region intact. In other words, RAI1 is dosage-sensitive. This provides evidence that it is the number of RAI1 copies present that affects the symptoms of PTLS and SMS. It is therefore believed that RAI1 is the critical gene involved in these disorders; One group has noted that, in a mouse model, the flanking genes in the duplicated segment were also overexpressed, suggesting some new candidates for analysis, including MFAP4, TTC19 and GJA12. == Diagnosis ==

The duplication involved in PTLS is usually large enough to be detected through G-banding alone, though there is a high false negative rate. == See also ==