title: Genotype-phenotype relationship in three cases with overlapping 19p13.12 microdeletions.
abstract: We describe the detailed clinical and molecular characterization of three patients (aged 7, 8(4/12) 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: mental retardation (MR), psychomotor and language delay, hearing impairment, brachycephaly, anteverted nares 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 all three patients; it was characterized by overactive disorder associated with MR and stereotyped movements (ICD10) in one patient and hyperactivity in the other two. As 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 patients.
authors.affiliation: Laboratorio di Citogenetica, E. Medea Scientific Institute, Lecco, Italy. clara.bonaglia@bp.lnf.it
authors.forename: Maria C
authors.initials: MC
authors.lastname: Bonaglia
authors.forename: Susan
authors.initials: S
authors.lastname: Marelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Novara
authors.forename: Simona
authors.initials: S
authors.lastname: Commodaro
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
authors.forename: Grazia
authors.initials: G
authors.lastname: Minardo
authors.forename: Luigi
authors.initials: L
authors.lastname: Memo
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mangold
authors.forename: Silvana
authors.initials: S
authors.lastname: Beri
authors.forename: Claudio
authors.initials: C
authors.lastname: Zucca
authors.forename: Daniele
authors.initials: D
authors.lastname: Brambilla
authors.forename: Massimo
authors.initials: M
authors.lastname: Molteni
authors.forename: Roberto
authors.initials: R
authors.lastname: Giorda
authors.forename: Ruthild G
authors.initials: RG
authors.lastname: Weber
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D003001:Cloning, Molecular; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D011247:Pregnancy; D017422:Sequence Analysis, DNA