临床推理:一位14岁的女孩与头痛、癫痫、和混乱

Images of the reported case (A) Brain CT shows cerebral infarction (triangle), subarachnoid hemorrhage (bold arrow), and thrombus of superior sagittal sinus (thin arrow). (B) CT venography (CTV) reveals cerebral venous sinus thrombosis (CVST) with filling defect of the right sigmoid sinus and right lateral sinuses (white arrow). (C) CTV after a month of treatment; the right sigmoid sinus and right lateral sinuses unobstructed but narrowed (white arrow). (D) X-ray suggests that joint space of bilateral wrist was narrowed. (E) The patient's long fingers. The circles show hyperpigmentation of skin, especially in the interphalangeal joints. (F) Histopathologic study of the patient's slightly darker skin reveals hyperkeratosis (yellow arrowhead) and verrucous hyperplasia in the basal layer of the epidermis (white arrowhead) (magnified 10 × 10 times under the microscope). (G) Pedigree of the family with homocystinuria. (H) Gene direct sequencing identified 2 novel compound heterozygous mutations: c.551T>C (p.L184P) and c.949A>G (p.R317G) (indicated by the red arrow). Ⅰ-1: Heterozygous mutations of c.949A>G, the c.551 TT is normal; Ⅰ-2: heterozygous mutations of c.551T>C, the c.949AA is normal; Ⅱ-1, Ⅱ-2: compound heterozygous mutations of c.551T>C and c.949A>G. (I) Orthologous protein sequence alignment of cystathionine β-synthase from different species. The mutated residue showing conservation is shaded in red. Red shaded amino acids proteins show that the 2 novel missense mutations occurred at highly conserved positions in these species. DD = Dictyostelium discodeum; HS = Homo sapiens; MM = Mus musculus; OC = Oryctolagus cuniculus; RN = Rattus norvegicus, splice isoform Ⅲ; SC = Saccharomyces cerevisiae; TC = Trypanosoma cruzi.