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HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI.

ABSTRACT: Biallelic mutations in the gene encoding HCLS-associated protein X-1 (HAX1) cause autosomal recessive severe congenital neutropenia (SCN). Some of these patients have neurological abnormalities including developmental delay, cognitive impairment, and/or epilepsy. Recent genotype-phenotype studies have shown that mutations in HAX1 affecting transcripts A (NM_006118.3) and B (NM_001018837.1) cause the phenotype of SCN with neurological impairment, while mutations affecting isoform A but not B lead to SCN without neurological aberrations. In this study, we identified a consanguineous family with two patients suffering from SCN and neurological disease caused by a novel, homozygous genomic deletion including exons 4-7 of the HAX1 gene. Quantitative MRI analyses showed generalized alterations in cerebral proton density in both of the patients, as well as in an additional unrelated patient with another HAX1 mutation (Arg86X) known to be associated with neurological manifestations. This study provides first in vivo evidence of aberrant neuroimaging findings associated with HAX1 deficiency in SCN patients.

SUBMITTER: Boztug K

PROVIDER: S-EPMC3164786 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI.

Boztug Kaan K Ding Xiao-Qi XQ Hartmann Hans H Ziesenitz Lena L Schäffer Alejandro A AA Diestelhorst Jana J Pfeifer Dietmar D Appaswamy Giridharan G Kehbel Sonja S Simon Thorsten T Al Jefri Abdullah A Lanfermann Heinrich H Klein Christoph C

American journal of medical genetics. Part A 20101201 12

Biallelic mutations in the gene encoding HCLS-associated protein X-1 (HAX1) cause autosomal recessive severe congenital neutropenia (SCN). Some of these patients have neurological abnormalities including developmental delay, cognitive impairment, and/or epilepsy. Recent genotype-phenotype studies have shown that mutations in HAX1 affecting transcripts A (NM_006118.3) and B (NM_001018837.1) cause the phenotype of SCN with neurological impairment, while mutations affecting isoform A but not B lead ...[more]

PMID: 21108402

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HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI.

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HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI.

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