ABSTRACT
Objective:To report the clinical phenotype and mutation site of a patient with grey matter heterotopia caused by a de novo heterozygous missense mutation in the TUBB2B gene, and to expand the phenotypic and mutational spectrum of TUBB2B mutations. Methods:One patient with TUBB2B mutation who presented to the Department of Neurology, the First Affiliated Hospital of Air Force Medical University in July 2017 was collected and analyzed for clinical features and mutation site, and a review of previous studies was performed. Results:The male patient started at the age of 18 and presented mainly with seizures, poor left-handed fine motor skills and poor spatial imagination. Magnetic resonance imaging showed nodular grey matter heterotopia in the right cerebral hemisphere, right frontoparietal-temporal localized cerebral gyrus, and cerebral sulcus shallow flat.The whole exon gene test suggested a heterozygous missense mutation in the TUBB2B gene: c.776 C>T (p.Pro259Leu), which was wild-type in both of his parents. The mutation site was located between the tubulin and tubulin-c structural domains and did not affect the function of the essential structural domain. After treatment with magnesium valproate in combination with levetiracetam, the patient′s seizure symptoms were significantly controlled and he has been seizure-free for 3 years now. Conclusions:The TUBB2B gene c.776 C>T (p.Pro259Leu) heterozygous missense mutation is a novel missense mutation causing grey matter heterotopia. The patient had a good prognosis, and the combination of two antiepileptic drugs resulted in complete seizure control.
ABSTRACT
Neurodegeneration with brain iron accumulation (NBIA) is a group of rare genetic diseases of nervous system. NBIA is characterized by varying degrees of abnormal iron metabolism and excessive iron deposition in brain tissue. The most common symptoms of NBIA are extrapyramidal symptoms. NBIA can also be associated with varying degrees of dysfunction of the pyramidal tract, cerebellum, peripheral nervous system, autonomic nervous system, mental cognition and vision functions. A patient with NBIA admitted to the Department of Neurology of Xijing Hospital in December 2020 was collected and analyzed for clinical features. Whole exome sequencing (WES) was employed to gene mutation screening, and pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics (ACMG) guideline. The patient was a 13-year-old male with a chronic course of disease that began at the age of 4. The first symptom was spastic gait. With the progress of the disease, the patient developed mental retardation, arrhythmia, coughing from drinking water and loss of vision. Magnetic resonance imaging of the head showed atrophy of the optic nerve and hypointensity signal in bilateral substantia nigra and globus pallidus on T 2WI, fluid attenuated inversion recovery sequency, diffusion weighted imaging and susceptibility weighted imaging without "tiger eye sign" which was commonly found in pantothenate kinase associated neurodegeneration. The homozygous mutation c.172G>A (p.Gly58Ser) was found through WES. The proband′s father and mother are cousins (inbreeding), carried heterozygous variation of this locus. This novel mutation was not reported in mutation database. According to ACMG guideline, C19orf12 gene c.172G>A (p.Gly58Ser) was identified for possible pathogenic mutations. The conservative prediction of this locus suggests high conservatism. The final diagnosis of the patient was mitochondrial membrane protein-associated neurodegeneration (MPAN,NBIA type 4). This finding enriched the known mutation database of MPAN and provided a basis for further study of the disease.
ABSTRACT
OBJECTIVE@#To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure.@*METHODS@#Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing.@*RESULTS@#Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations.@*CONCLUSION@#Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.