PIGH deficiency can be associated with severe neurodevelopmental and skeletal manifestations.
Clin Genet
; 99(2): 313-317, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-33156547
ABSTRACT
Phosphatidylinositol Glycan Anchor Biosynthesis class H (PIGH) is an essential player in the glycosylphosphatidylinositol (GPI) synthesis, an anchor for numerous cell membrane-bound proteins. PIGH deficiency is a newly described and rare disorder associated with developmental delay, seizures and behavioral difficulties. Herein, we report three new unrelated families with two different bi-allelic PIGH variants, including one new variant p.(Arg163Trp) which seems associated with a more severe phenotype. The common clinical features in all affected individuals are developmental delay/intellectual disability and hypotonia. Variable clinical features include seizures, autism spectrum disorder, apraxia, severe language delay, dysarthria, feeding difficulties, facial dysmorphisms, microcephaly, strabismus, and musculoskeletal anomalies. The two siblings homozygous for the p.(Arg163Trp) variant have severe symptoms including profound psychomotor retardation, intractable seizures, multiple bone fractures, scoliosis, loss of independent ambulation, and delayed myelination on brain MRI. Serum iron levels were significantly elevated in one individual. All tested individuals with PIGH deficiency had normal alkaline phosphatase and CD16, a GPI-anchored protein (GPI-AP), was found to be decreased by 60% on granulocytes from one individual. This study expands the PIGH deficiency phenotype range toward the severe end of the spectrum with the identification of a novel pathogenic variant.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Anomalías Múltiples
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Enfermedades del Desarrollo Óseo
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Trastornos del Neurodesarrollo
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Proteínas de la Membrana
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Clin Genet
Año:
2021
Tipo del documento:
Article
País de afiliación:
Canadá