Genotype-phenotype relationship in three cases with overlapping 19p13.12 microdeletions.

Maria Clara Bonaglia (1) , Susan Marelli (1) , Francesca Novara (1) , Simona Commodaro (1) , Renato Borgatti (1) , Grazia Mingardo (1) , Luigi Memo (1) , Elisabeth Mangold (1) , Silvana Beri (1) , Claudio Zucca (1) , Daniele Brambilla (1) , Massimo Molteni (1) , Roberto Giorda (1) , Ruthild G. Weber (1) , Orsetta Zuffardi (1)

1 Cytogenetics

We describe the detailed clinical and molecular characterization of three patients (aged 16 months, 7 and 31 years) with overlapping microdeletions in 19p13.12, extending to 19p13.13 in two cases. The patients share the following clinical features with a recently reported 10-year-old girl with a 19p13.12 microdeletion (Jensen et al., 2009): mental retardation (MR), psychomotor and language delay, hearing impairment, brachycephaly, anteverted nares, long philtrum, and ear malformations. All patients share a 359 kb deleted region in 19p13.12 harboring six genes (LPHN1, DDX39, CD97, PKN1, PTGER1, and GIPC1), several of which may be MR candidates because of their function and expression pattern. LPHN1 and PKN1 are the most appealing; LPHN1 for its interaction with Shank family proteins, and PKN1 because it is involved in a variety of functions in neurons, including cytoskeletal organization. Haploinsufficiency of GIPC1 may contribute to hearing impairment for its interaction with myosin VI. A behavioral phenotype was observed in the two oldest patients; it was characterized by overactive disorder associated with MR and stereotyped movements (ICD10) in one patient and difficult-to-manage hyper-activity in the other. Since Ptger1-null mice show behavioral inhibition and impulsive aggression with defective social interaction, PTGER1 haploinsufficiency may be responsible for the behavioral traits observed in these two patients.

Mots clés: 19p13.12 microdeletion; mental retardation; hearing loss

Maria Clara Bonaglia, Susan Marelli, Francesca Novara, Simona Commodaro, Renato Borgatti, et al.. Genotype-phenotype relationship in three cases with overlapping 19p13.12 microdeletions.. European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.115⟩. ⟨hal-00558092⟩