ClinVar

In 4 unrelated patients with hypomyelinating leukodystrophy-16 (HLD16; 617964) Simons et al. (2017) identified a heterozygous c.754G-A transition (c.754G-A, NM_001134232) in exon 8 of the TMEM106B gene, resulting in an asp252-to-asn (D252N) substitution at a highly conserved residue in the intraluminal part of the protein. The mutation, which was identified by trio-based whole-exome or whole-genome sequencing, was not found in the dbSNP, ExAC, or gnomAD databases. The mutation occurred de novo in 3 patients, but the mildly affected father of 1 of the patients (patient 3) was mosaic for the mutation. Functional studies of the variant and studies of patient cells were not performed.

Yan et al. (2018) identified a de novo heterozygous D252N mutation in the TMEM106B gene in a 3-year-old girl of Chinese descent with HLD16. The mutation was found by trio whole-exome sequencing and confirmed by Sanger sequencing. Functional studies of the variant and studies of patient cells were not performed, but Yan et al. (2018) noted that the mutation occurred at a CpG dinucleotide, suggesting that it is a recurrent mutation due to a hotspot within the gene.