Abstract
Heterozygous HTRA1 mutations, recently, have been reported as a cause of autosomal dominant hereditary cerebral small vessel disease (CSVD). We herein describe clinical and neuroimaging findings in two familial CSVD with two different heterozygous HTRA1 mutations. Detailed clinical and neuroimaging examination were conducted in probands and their available family members. A next-generation sequencing-based comprehensive gene panel was used to investigate their causative mutations. A novel heterozygous missense variant c.527T>C (p.V176A) and a novel heterozygous nonsense variant c.589C>T (p.R197X) in HTRA1 gene were detected in probands of family 1 and family 2, respectively. Co-segregation analysis in family 1 showed eight family members were mutation carriers. All alive male patients showed typical clinical and neuroimaging features of CSVD. All alive female mutation carriers were clinical or neuroimaging asymptomatic. Screening of HTRA1 should be considered in patients with familial CSVD. A male predominance may exist in patients with heterozygous HTRA1 mutations and need to be further investigated.
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We are indebted to the patients and their family members for participation in this project.
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This study was supported by the National Natural Science Foundation of China (Proj. No. 81201722).
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This study was approved by the Research Ethics Committees of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. All patients and their family members provided written informed consent for participation in this study.
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Zhang, Wy., Xie, F. & Lu, Pl. Two novel heterozygous HTRA1 mutations in two pedigrees with cerebral small vessel disease families. Neurol Sci 39, 497–501 (2018). https://doi.org/10.1007/s10072-017-3231-z
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DOI: https://doi.org/10.1007/s10072-017-3231-z