Details

Autor(en) / Beteiligte

• Thompson, Miles D
• Li, Xueying
• Spencer-Manzon, Michele
• Andrade, Danielle M
• Murakami, Yoshiko
• Kinoshita, Taroh
• Carpenter, Thomas O

Titel

Excluding Digenic Inheritance of PGAP2 and PGAP3 Variants in Mabry Syndrome (OMIM 239300) Patient: Phenotypic Spectrum Associated with PGAP2 Gene Variants in Hyperphosphatasia with Mental Retardation Syndrome-3 (HPMRS3)

Ist Teil von

• Genes, 2023-01, Vol.14 (2), p.359

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We present a case report of a child with features of hyperphosphatasia with neurologic deficit (HPMRS) or Mabry syndrome (MIM 239300) with variants of unknown significance in two post-GPI attachments to proteins genes, and , that underlie HPMRS 3 and 4. In addition to HPMRS 3 and 4, disruption of four phosphatidylinositol glycan (PIG) biosynthesis genes, , , and , result in HPMRS 1, 2, 5 and 6, respectively. Targeted exome panel sequencing identified homozygous variants of unknown significance (VUS) in c:284A>G and c:259G>A. To assay the pathogenicity of these variants, we conducted a rescue assay in and deficient CHO cell lines. Using a strong (pME) promoter, the variant did not rescue activity in CHO cells and the protein was not detected. Flow cytometric analysis showed that CD59 and CD55 expression on the PGAP2 deficient cell line was not restored by variant . By contrast, activity of the variant was similar to wild-type. For this patient with Mabry syndrome, the phenotype is likely to be predominantly HPMRS3: resulting from autosomal recessive inheritance of NM_001256240.2 c:284A>G, p.Tyr95Cys. We discuss strategies for establishing evidence for putative digenic inheritance in GPI deficiency disorders.