Identification of Novel Mutations in Chinese Patients with Metachromatic Leukodystrophy.

Objective: Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA) that leads to severe physiologic and developmental problems. Our study is aimed at elucidating the clinical and genetic characteristics of Chinese MLD patients.

Methods: Clinical data of 21 MLD patients was collected. All coding exons of and their flanking intronic sequences were amplified by polymerase chain reaction and subjected to direct sequencing.

Results: All 21 patients were diagnosed with MLD clinically and genetically, out of which 17 patients were late infantile and 4 were juvenile types. A total of 34 mutations, including 28 novel mutations (22 missense, 1 splicing, 1 nonsense, 3 small insertions, and 1 small deletion mutation) and 6 known mutations (5 missense and 1 small insertion mutation), were identified. Prenatal diagnosis was performed for four pedigrees. One fetus was a patient, two fetuses were carriers, and two were wild type.

Conclusions: The present study discovered 28 novel mutations and widely expanded the mutation spectrum of . Four successful prenatal diagnoses provided critical information for MLD families.