Novel <i>RNF113A</i> Variant Underlying X‐Linked Trichothiodystrophy With Presumed Mosaicism in an Unaffected Mother

Trichothiodystrophies (TTDs) are a group of disorders that have been characterized by sparse, brittle, and sulfur deficient hair that showed a "tiger-tail" banding pattern. Though the majority of TTDs are inherited in an autosomal recessive pattern, RNF113A related trichothiodystrophy is X-linked. RNF113A-related TTD has been associated with a non-photosensitive trichothiodystrophy, characterized by intellectual disability, microcephaly, growth restriction and failure, genital abnormalities, endocrine abnormalities, recurrent infections, and abnormal brain magnetic resonance imaging (MRI). To date, six individuals have been described with RNF113A-related TTD. Here we describe two brothers in their 30's with a novel hemizygous variant c.635G>A p.Gly212Asp in the RNF113A gene, which is not present in the tissues tested in their mother. Protein modeling suggests significant structural alteration. The brothers are the oldest known affected individuals and have features consistent with X-linked trichothiodystrophy including intellectual disability, microcephaly, growth failure, dysmorphic features, severe myopia and tiger-tail banding pattern. Absence of endocrinological abnormalities, recurrent infections, genital abnormalities, and abnormal MRI showed that these are not universal findings of RNF113A related trichothiodystrophy. Given that absence of the variant in the patients' mother, we presume the mother to have low level somatic mosaicism or germline mosaicism for the variant. This highlights the importance of genetic counseling for accurate recurrence risks and warranted reproductive testing for parents and female siblings of affected individuals with presumed de novo variants.