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Hypergonadotropic hypogonadism and hypersegmented neutrophils in a patient with ataxia‐telangiectasia‐like disorder: Potential diagnostic clues?
Author(s) -
Yoshida Takeshi,
Awaya Tomonari,
Shibata Minoru,
Kato Takeo,
Numabe Hironao,
Kobayashi Junya,
Komatsu Kenshi,
Heike Toshio
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36546
Subject(s) - ataxia telangiectasia , hypergonadotropic hypogonadism , ataxia , missense mutation , spinocerebellar ataxia , atrophy , medicine , mutation , endocrinology , genetics , gene , biology , psychiatry , hormone , dna damage , dna
Ataxia‐telangiectasia‐like disorder (ATLD) is a rare autosomal recessive disorder, and has symptoms similar to ataxia‐telangiectasia (AT). ATLD is caused by mutations in the MRE11 gene, involved in DNA double‐strand break repair (DSBR). In contrast to AT, ATLD patients lack key clinical features, such as telangiectasia or immunodeficiency, and are therefore difficult to be diagnosed. We report a female ATLD patient presenting with hypergonadotropic hypogonadism and hypersegmented neutrophils, previously undescribed features in this disorder, and potential diagnostic clues to differentiate ATLD from other conditions. The patient showed slowly progressive cerebellar ataxia from 2 years of age, and MRI revealed atrophy of the cerebellum, oculomotor apraxia, mild cognitive impairment, writing dystonia, hypergonadotropic hypogonadism with primary amenorrhea, and hypersegmented neutrophils. Western blot assay demonstrated total loss of MRE11 and reduction of ATM‐dependent phosphorylation; thus, we diagnosed ATLD. Genetically, a novel missense mutation (c.140C>T) was detected in the MRE11 gene, but no other mutation was found in the patient. Our presenting patient suggests that impaired DSBR may be associated with hypergonadotropic hypogonadism and neutrophil hypersegmentation. In conclusion, when assessing patients with ataxia of unknown cause, ATLD should be considered, and the gonadal state and peripheral blood smear samples evaluated. © 2014 Wiley Periodicals, Inc.