摘要
We present the clinical symptoms of four patients which resulted from mutation s in the p63 gene. The variability of the phenotype includes an isolated split h and/foot malformation (patient 1), split hand/foot malformation with ectodermal defects (patients 2 and 3), and ectodermal dysplasia as a main feature of the an kyloblepharon-ectodermal defects-cleft lip/-palate (AEC) syndrome (patient 4) . Different phenotypes of p63-associated disorders and the correlation between the phenotype and genotype are discussed.
Background: Although homozygous mutations in the PTEN- induced putative kinase 1 (PINK1) gene have been unequivocally associated with early- onset Parkinson disease (PD), the role of single heterozygous PINK1 mutations is less clear. Objective: To investigate the role of homozygous and heterozygous PINK1 mutations in a large German pedigree (family W). Design: Mutation analysis of PINK1 and results of standardized neurological and motor examination by 3 independent movement disorder specialists, including blinded video rating. Settings: University of Lü beck. Participants: Twenty family members. Main Outcome Measures: The PINK1 genotype and PD status of all family members. Results: The index patient of family W carried a homozygous nonsense mutation (c.1366C>T; p.Q456X) and presented with a phenotype closely resembling idiopathic PD but with an onset at 39 years of age. The family included a total of 4 affected homozygous members (age, 60- 71 years; age at onset, 39- 61 years), 6 members with slight or mild signs of PD (affected) and a heterozygous mutation (age, 31- 49 years), and 5 unaffected heterozygous mutation carriers (age, 34- 44 years). Although none of the heterozygous affected family members was aware of their signs (asymptomatic), the clinical findings were unequivocal and predominantly or exclusively present on their dominant right- hand side, eg, unilaterally reduced or absent arm swing and unilateral rigidity. The heterozygous members were all considerably younger than the affected homozygous mutation carriers. Conclusions: Heterozygous PINK1 mutations may predispose to PD, as was previously suggested by the presence of dopamine hypometabolism in asymptomatic mutation carriers. Long- term follow- up of our large family W provides an excellent opportunity to further evaluate the role of single heterozygous PINK1 mutations later in life, which will have major implications on genetic counseling.
