Bi-allelic POLR3A null variants cause autosomal recessive leukodystrophy, hypomyelinating, 7

Wiedemann-Rautenstrauch syndrome (WDRTS) is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, hypotonia, and variable mental impairment. We described a detailed clinical manifestation of pediatric patient with compound heterozygous null variants of POLR3A as she gets older. At 18 months, she showed seizure-like activity that was difficult to distinguish from dystonia and development was regressed. She showed spasticity that affects the entire body and could not speak any words. Her diagnosis was permuted Leigh-like syndrome to leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotrophic hypodonadism (4H syndrome, OMIM # 607684). As a result, bi-allelic POLR3A null variants, c.1771-6C>G and c.1650_1661del (Nucleotide ID: NM_007055.3) were best candidate as cause of autosomal recessive WDRTS. Particularly, POLR3A c.1771-6C>G (rs115020338) variants were reported with minor allele frequency of 0.00005581 and to be associated with POLR3-related leukodystrophy in a Chinese family .