دانلود رایگان مقاله انگلیسی Hyperphosphatasia با سندرم عقب ماندگی ذهنی، گسترش فنوتیپ اختلالات مرتبط با PIGL - الزویر 2018

ABSTRACT

Hypomorphic mutations in six different genes involved in the glycosylphosphatidylinositol (GPI) biogenesis pathway are linked to Mabry syndrome (hyperphosphatasia with mental retardation syndrome, HPMRS). This report on the third affected family with a HPMRS phenotype caused by mutations in PIGL, confirming the seventh GPI biogenesis gene linked to HPMRS. Two siblings presented with the main features of HPMRS; developmental delay, cognitive impairment, seizure disorder, skeletal deformities, and high alkaline phosphatase. We identified two heterozygous mutations in the PIGL gene (P.Trp20Ter and p.Arg88Cys). PIGL mutations have been linked to another distinctive neuroectodermal disorder: CHIME syndrome. The clinical picture of our patients expands the spectrum of PIGL-related phenotypes.

4. Discussion

In 1970, Mabry et al. described a unique syndrome comprised of severe cognitive impairment, seizures, various neurologic deficits, and elevated serum ALP [6]. This syndrome was acronymed HPMRS1(OMIM: 239300) [7] and linked to mutations in the PIGV gene, which is involved in the early steps of GPI anchor assembly [8]. Subsequently, other pathogenic defects in genes involved in either GPI anchor assembly or maturation were linked to the same phenotype. [Table 1].

The PIGL gene is responsible for the second step of GPI biosynthesis. Mutations in this gene were initially reported in seven cases presenting with CHIME syndrome. CHIME (OMIM: 280000, ocular Colobomas, Heart defect, Ichthyosis, Mental Retardation, and abnormal Ears or Epilepsy) was first described clinically by Zunich et al. in 1983, acronymed by Shashi et al. in 1995, and linked to PIGL mutations by Ng et al. in 2012. All patients presented the main features of CHIME syndrome plus a variable combination of facial dysmorphism such as brachycephaly, flat and broad nasal root, short philtrum, hypertelorism, cloudy corneas, overfolded helices, wide mouth, full lips, cleft palate, and abnormal dentation. Mildly elevated alkaline phosphatase was reported in only one patient who presented with a clinical phenotype of CHIME syndrome (not molecularly confirmed) in the setting of acute lymphocytic leukemia [5,9–12].