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Aminoacylase I deficiency due to ACY1 mRNA exon skipping
Author(s) -
Ferri L.,
Funghini S.,
Fioravanti A.,
Biondi E.G.,
la Marca G.,
Guerrini R.,
Donati M.A.,
Morrone A.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12297
Subject(s) - hypotonia , exon , inborn error of metabolism , intellectual disability , biology , genetics , medicine , endocrinology , microbiology and biotechnology , gene
Aminoacylase 1 ( ACY1 ) deficiency is a rare inborn error of metabolism of which less than 20 observations have been described. Patients exhibit urinary excretion of specific N ‐acetyl amino acids and manifest a heterogeneous clinical spectrum including intellectual disability, motor delay, seizures, moderate to severe mental retardation, absent speech, growth delay, muscular hypotonia and autistic features. Here, we report the case of ACY1 enzyme deficiency in a 6‐year‐old girl presenting severe intellectual disability, motor retardation, absence of spontaneous locomotor activity and severe speech delay. Urinary excretion of N ‐acetylated amino acids was present. Mutational analysis of ACY1 gene identified the new homozygous c.1001_1001+5del6 mutation, which alters the mRNA transcription leading to exon 13 skipping and inclusion of a premature stop codon (p. Lys308Glufs *7). A quantitative fluorescent multiplex‐polymerase chain reaction ( QFM‐PCR ) assay has been set up and confirmed homozygosity of the mutation in the patient's DNA . Biochemical analysis showed absence of ACY1 enzyme activity in the patient's fibroblasts. The structure of the mutated protein has been defined by homology modeling (HM). Our data endorse the hypothesis of a link between this inborn error of metabolism and the neurological manifestations observed in patients with ACY1 deficiency.