[P1-190] Identification of Two Novel Mutations in TUBB4A and Prenatal Diagnosis in Chinese Patients with Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC, OMIM 612438) is a rare autosomal dominant disease caused by mutations in TUBB4A. This study was aimed to clarify clinical and genetic features of 7 Chinese H-ABC patients. Clinical information and peripheral venous blood of 7 H-ABC patients and their parents were collected. Next generation sequencing with a gene panel related to leukodystrophy including TUBB4A and Sanger-sequencing of the corresponding sites for both probands and their parents were performed to make genetic diagnosis. Genomic DNA of fetuses was extracted from amniotic fluid and corresponding sites were sequenced by Sanger-sequencing. Maternal cell contamination was excluded with microsatellite analysis. In this study, clinical and genetic analysis was performed in 7 Chinese H-ABC patients first. Development delay, motor deterioration, extrapyramidal signs and ataxia were found in 7(100%), 7(100%), 7(100%), at least 4(57.1%) patients, respectively. Hypomyelination, basal ganglia atrophy and cerebellum atrophy were detected in cranial MRI of 7(100%), 5(71.4%), 5(71.4%) patients, respectively. 7 (100%) patients were clinically diagnosed with H-ABC and genetically diagnosed with 5 mutations in TUBB4A consisting of 3 reported mutations (c.745G>A(p.D249N), c.785G>A(p.R262H), c.731G>A(p.G244D)) and 2 novel (c.1190G>T(p.W397L), c.538G>A(p.V180M)) mutations. Prenatal molecular diagnosis was performed successfully in 2 (Pt1, Pt6) families, and neither corresponding mutations nor MCC were detected in the fetuses. This research made clinical and genetic analysis for Chinese H-ABC patients, discovering clinical features of Chinese H-ABC patients, identifying 2 novel mutations, expanding mutation spectrums of TUBB4A. It was the first time to make prenatal molecular diagnosis for 2 H-ABC families