分子与遗传医学

Angelman syndrome is a rare neurogenetic disorder that usually is clinically associated with global developmental delay including absence of speech, seizures, ataxic gait and frequent smiling. Its genetic bases is complex even though normally it may be attributed to epigenetic alterations of chromosomal region 15q11.2~13. We present a girl of 7 years who was referred with delayed neurological development, speech impairment, and some minor facial anomalies, such as microcephaly and open mouth. Clinical symptoms suggested the diagnosis of Angelman syndrome. Cytogenetic results showed a karyotype 47,XX,+ mar in all 30 analyzed metaphases. Fluorescence in situ hybridization studies revealed origin and size of the small supernumerary marker chromosome as an inv dup(15)(q11.1) not including any euchromatin. Microsatellite analyses revealed that both chromosomes were derived exclusively from the father and thus the clinical diagnosis of Angelman syndrome was supported. Angelman syndrome caused by paternal uniparental disomy is rare, although it has been reported by other researchers, associated with supernumerary marker chromosome as well as other complex chromosomal rearrangements. It has to be always in mind also for genetic counseling that chromosomal aberrations can be a hint on epigenetic alterations. This article reviews eight previously published comparable cases of literature.

Mutations in the glucocerebrosidase gene (GBA) are a common genetic risk factor for Dementia with Lewy Bodies (DLB). Hereby, we describe an Italian family with three DLB relatives harboring the D419H GBA variant. The pedigree analysis indicates a dominant inheritance pattern, suggesting that heterozygous GBA mutations may differently affect the risk of Parkinson-dementia syndromes. This should be taken into account for genetic counseling in relatives of patients with GBA associated Parkinson’s Disease/DLB.