Identification of a Novel Nonsense Mutation in PLA2G6 and Prenatal Diagnosis in a Chinese Family With Infantile Neuroaxonal Dystrophy
Creators: name: Zou, Yongyi
Publisher: name: figshare
Year: 2022
Subjects: subject: 110311 Medical Genetics (excl. Cancer Genetics)
subject: FOS: Basic medicine

description: <strong>Sanger sequencing validation of exon3 and exon14 in Pla2g6 gene.</strong> Two Chinese siblings who were children of a non-consanguineous healthy couple were admitted to the pediatric department in Jiangxi Maternal and Child Hospital (Jiangxi, China). They both presented with delayed motor and intellectual development. The whole pedigree had no significant family history of genetic diseases. The two siblings were born at term after an uneventful pregnancy and delivery. No feeding difficulties or hypotonia were noticed in both of them at birth and they achieved normal developmental milestones. According to the description of their parents, the elder brother presented with slurred speech and walking difficulty at the age of two. After an observation period for physical condition, the proband was taken to the pediatric department and performed with brain magnetic resonance imaging (MRI), as well as electrocardiogram(ECG) and electroencephalogram(EEG) examinations when he was 2.5 years old. The MRI showed typical bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas, indicating periventricular leukomalacia and myelin sheath dysplasia, while ECG and EEG showed no significant abnormality. Despite of rehabilitation therapy for nearly one year, the proband demonstrated more severer symptoms than before. He even had difficulty in standing securely and expressing himself clearly. Dysarthria , hypalgesia, emotional instability, impaired concentration ,scissors gait and developmental retardation and regression were also observed by the pediatrician. His muscle strength is decreased in Grade 3 and showed high muscle tension, while tendon reflexes are nomal. No strabismus, nystagmus or hearing loss were observed. A second MRI and EEG examination was performed again when he was 3.5 years old. The MRI indicated bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular white matter with slightly increased areas than his initial MRI test. Furthermore, his second MRI examination showed the presence of cerebellar atrophy, while EEG examination still showed no abnormality. When the proband was 4.8 years old, the proband was perforemed a third MRI and the findings showed good demarcations between cerebral white and gray matter, normal corpus callosum shape, no presence of brain iron accumulation or cerebellar T2-hyperintensity. However, multiple abnormal signal focuses in bilateral frontal parietal white matter, claval hypertrophy and cerebellar atrophy were observed. When the proband is six years old, he lost his total ability of walking or standing and a wheelchair is the necessity of his life. His younger brother presented clinical manifestations similar to him, but his slurred speech started at the age of 18 months, which was an earlier age. At the age of four, this younger brother showed difficulty in walking and gait abnormalities. 1-1 indicates the father (exon3) 1-2 indicates the mother (exon3) 1-3 indicates the proband (exon3) 1-4 indicates the younger brother (exon3) XJ YSI E3 indicates the fetal samples (exon3) 2-1 indicates the father (exon14) 2-2 indicates the mother (exon14) 2-3 indicates the proband (exon14) 2-4 indicates the younger brother (exon14) XJ YSI E14 indicates the fetal samples (exon14)