A case of inherited glycosylphosphatidylinositol deficiency caused by PGAP3 variant with uniparental isodisomy on chromosome 17

Autor: Takeo Mukai, Shota Kato, Hiroyuki Tanaka, Yukiko Kuroda, Hiroki Kitaoka, Atsushi Ito, Yoshihiko Shitara, Kohei Kashima, Hirokazu Takami, Naoto Takahashi, Motohiro Kato
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Molecular Genetics & Genomic Medicine, Vol 12, Iss 7, Pp n/a-n/a (2024)
Druh dokumentu: article
ISSN: 2324-9269
DOI: 10.1002/mgg3.2452
Popis: Abstract Background Inherited glycosylphosphatidylinositol (GPI) deficiency is an autosomal recessive disease and a set of syndromes caused by different genes involved in the biosynthesis of phosphatidylinositol characterized by severe cognitive disability, elevated serum alkaline phosphatase (ALP) levels, and distinct facial features. This report presents a patient with inherited GPI deficiency caused by a homozygous frameshift variant of PGAP3 due to uniparental isodisomy (UPiD) on chromosome 17. Method Clinical characteristics of the patient were collected. Microarray analysis followed by adaptive sampling sequencing targeting chromosome 17 was used for the identification of variants. Sanger sequencing was used to confirm the variant in the target region. Results The patient was born at 38 weeks of gestation with a birthweight of 3893 g. He had a distinctive facial appearance with hypertelorism, wide nasal bridge, and cleft soft palate. Postnatal head magnetic resonance imaging revealed a Blake's pouch cyst. The serum ALP level was 940 IU/L at birth and increased to 1781 IU/L at 28 days of age. Microarray analysis revealed region of homozygosity in nearly the entire region of chromosome 17, leading to the diagnosis of UPiD. Adaptive sampling sequencing targeting chromosome 17 confirmed the homozygous variant NM_033419:c.778dupG (p.Val260Glyfs*14) in the PGAP3 gene, resulting in a diagnosis of inherited GPI deficiency. Conclusion This is the first report of inherited GPI deficiency caused by UPiD. Inherited GPI deficiency must be considered in patients with unexplained hyperphosphatasemia.
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