| [PMID]: | 25706356 |
| [Au] Autor: | Fujiwara I; Murakami Y; Niihori T; Kanno J; Hakoda A; Sakamoto O; Okamoto N; Funayama R; Nagashima T; Nakayama K; Kinoshita T; Kure S; Matsubara Y; Aoki Y |
| [Ad] Endereço: | Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan. |
| [Ti] Título: | Mutations in PIGL in a patient with Mabry syndrome. |
| [So] Source: | Am J Med Genet A;167A(4):777-85, 2015 Apr. |
| [Is] ISSN: | 1552-4833 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Mabry syndrome, hyperphosphatasia mental retardation syndrome (HPMRS), is an autosomal recessive disease characterized by increased serum levels of alkaline phosphatase (ALP), severe developmental delay, intellectual disability, and seizures. Recent studies have revealed mutations in PIGV, PIGW, PIGO, PGAP2, and PGAP3 (genes that encode molecules of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway) in patients with HPMRS. We performed whole-exome sequencing of a patient with severe intellectual disability, distinctive facial appearance, fragile nails, and persistent increased serum levels of ALP. The result revealed a compound heterozygote with a 13-bp deletion in exon 1 (c.36_48del) and a two-base deletion in exon 2 (c.254_255del) in phosphatidylinositol glycan anchor, class L (PIGL) that caused frameshifts resulting in premature terminations. The 13-bp deletion was inherited from the father, and the two-base deletion was inherited from the mother. Expressing c.36_48del or c.254_255del cDNA with an HA-tag at the C- or N-terminus in PIGL-deficient CHO cells only partially restored the surface expression of GPI-anchored proteins (GPI-APs). Nonsynonymous changes or frameshift mutations in PIGL have been identified in patients with CHIME syndrome, a rare autosomal recessive disorder characterized by colobomas, congenital heart defects, early onset migratory ichthyosiform dermatosis, intellectual disability, and ear abnormalities. Our patient did not have colobomas, congenital heart defects, or early onset migratory ichthyosiform dermatosis and hence was diagnosed with HPMRS, and not CHIME syndrome. These results suggest that frameshift mutations that result in premature termination in PIGL cause a phenotype that is consistent with HPMRS. |
| [Mh] Termos MeSH primário: |
Anormalidades Múltiplas/diagnóstico
Deficiência Intelectual/diagnóstico
N-Acetilglucosaminiltransferases/genética
Distúrbios do Metabolismo do Fósforo/diagnóstico
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| [Mh] Termos MeSH secundário: |
Anormalidades Múltiplas/genética
Sequência de Aminoácidos
Animais
Sequência de Bases
Células CHO
Pré-Escolar
Cricetinae
Cricetulus
Análise Mutacional de DNA
Feminino
Seres Humanos
Deficiência Intelectual/genética
Dados de Sequência Molecular
Distúrbios do Metabolismo do Fósforo/genética
Deleção de Sequência
Síndrome
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| [Pt] Tipo de publicação: | CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 3.5.1.89 (PIGL protein, human) |
| [Em] Mês de entrada: | 1512 |
| [Cu] Atualização por classe: | 150330 |
[Lr] Data última revisão:
| 150330 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 150224 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1002/ajmg.a.36987 |
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