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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Muzammal, M; Ali, MZ; Brugger, B; Blatterer, J; Ahmad, S; Taj, S; Shah, SK; Khan, S; Enzinger, C; Petek, E; Wagner, K; Khan, MA; Windpassinger, C.
A novel protein truncating mutation in L2HGDH causes L-2-hydroxyglutaric aciduria in a consanguineous Pakistani family.
Metab Brain Dis. 2022; 37(1):243-252 Doi: 10.1007/s11011-021-00832-2 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Windpassinger Christian
Co-Autor*innen der Med Uni Graz
Blatterer Jasmin
Brugger Beatrice Anna
Enzinger Christian
Petek Erwin
Wagner Klaus

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BACKGROUND: L-2-hydroxyglutaric aciduria (L2HGA) is a rare neurometabolic disorder that occurs due to accumulation of L-2-hydroxyglutaric acid in the cerebrospinal fluid (CSF), plasma and urine. The clinical manifestation of L2HGA includes intellectual disability, cerebellar ataxia, epilepsy, speech problems and macrocephaly. METHODS: In the present study, we ascertained a multigenerational consanguineous Pakistani family with 5 affected individuals. Clinical studies were performed through biochemical tests and brain CT scan. Locus mapping was carried out through genome-wide SNP genotyping, whole exome sequencing and Sanger sequencing. For in silico studies protein structural modeling and docking was done using I-TASSER, Cluspro and AutoDock VINA tools. RESULTS: Affected individuals presented with cognitive impairment, gait disturbance, speech difficulties and psychomotor delay. Radiologic analysis of a male patient revealed leukoaraiosis with hypoattenuation of cerebral white matter, suggestive of hypomyelination. Homozygosity mapping in this family revealed a linkage region on chromosome 14 between markers rs2039791 and rs781354. Subsequent whole exome analysis identified a novel frameshift mutation NM_024884.3:c.180delG, p.(Ala62Profs*24) in the second exon of L2HGDH. Sanger sequencing confirmed segregation of this mutation with the disease phenotype. The identification of the most N-terminal loss of function mutation published thus far further expands the mutational spectrum of L2HGDH.
Find related publications in this database (using NLM MeSH Indexing)
Alcohol Oxidoreductases - genetics
Brain Diseases, Metabolic, Inborn - administration & dosage
Consanguinity - administration & dosage
Humans - administration & dosage
Male - administration & dosage
Mutation - genetics
Pakistan - administration & dosage

Find related publications in this database (Keywords)
L-2-hydroxyglutaric aciduria
Whole exome sequencing
Intellectual disability
N-terminal frameshift mutation
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