PGAP3-related hyperphosphatasia with mental retardation syndrome: Report of 10 new patients and a homozygous founder mutation.

PGAP3-related hyperphosphatasia with mental retardation syndrome: Report of 10 new patients and a homozygous founder mutation. Clin Genet. 2017 Apr 08;: Authors: Abdel-Hamid MS, Issa MY, Otaify GA, Abdel-Ghafar SF, Elbendary HM, Zaki MS Abstract Hyperphosphatasia with mental retardation syndrome (HPMRS) is caused by recessive mutations in genes involved in the glycosylphosphatidylinsitol pathway, including PGAP3. Herein, we describe 10 patients from 8 Egyptian families presenting with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Eight patients had cleft palate, four had postnatal microcephaly and five had seizures. Neuroimaging findings showed thin corpus callosum in 9 patients, mild ventriculomegaly in 3 patients and variable degrees of cerebellar vermis hypoplasia in 4 patients, a finding not previously reported in patients with HPMRS. Additional manifestations included double row teeth, hypogenitalism and congenital heart disease. Biallelic loss of function mutations in the PGAP3 gene were detected in all patients. Nine patients were homozygous for the c.402dupC (p.M135Hfs*28) mutation strongly suggesting a founder effect. On the other hand, one patient had a novel mutation, c.817_820delGACT (p.D273Sfs*37). To our knowledge, this is the largest series of patients with HPMRS from same ethnic group. Our results reinforce the distinct clinical and facial features...
Source: Clinical Genetics - Category: Genetics & Stem Cells Authors: Tags: Clin Genet Source Type: research