A pedigree analysis of LMNB1-related adult-onset autosomal dominant leukodystrophy
Objective To summarize the clinical and imaging features of LMNB1-related adult-onset autosomal dominant leukodystrophy (ADLD),and analyze the pathogenic variation. Methods An ADLD patient diagnosed in Xuanwu Hospital,Capital Medical University in November,2023 was selected,and clinical and imaging data of the proband and other paitents in the family were collected. Whole-exome sequencing (WES) and analysis were completed for the proband and the result was confirmed using multiplex ligation-dependent probe amplification (MLPA) assay,and pathogenicity analysis and phenotype matching analysis were carried out according to the results. Results The patient (proband) was a 44-year-old male,who was treated for defecation disorder for three years and weakness of both lower limbs for more than two years. The genetic test showed duplication of 1-11 coding exons in the LMNB1 gene,which was classified as pathogenic variation,and the phenotype matched with ADLD. The first symptoms of the proband (Ⅲ:9) and Ⅲ:6 were autonomic dysfunction,which was a typical manifestation of ADLD. However,Ⅱ:11 had head tremor as the first symptom,which was different from other patients. Conclusions A duplication of 1-11 coding exons in the LMNB1 gene is identified,which accords with autosomal dominant inheritance pattern. Adult patients start with autonomic dysfunction,and then involve the cerebellum and pyramidal tract,and when MRI shows extensive symmetrical white matter lesions and spinal cord atrophy,ADLD should be considered,and LMNB1 gene testing is recommended.
LMNB1 genecopy number variation (CNV)adult-onset autosomal dominant leukodystrophy (ADLD)
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