Novel pathogenic RECQL4 variants in Chinese patients with Rothmund-Thomson syndrome.

BACKGROUND: Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder mainly characterized by cutaneous poikiloderma, sparse hair, short stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases. METHODS: Three Chinese patients from two unrelated families were enrolled for clinical evaluation. Targeted next-generation sequencing (NGS) using a custom panel consisting of 705 short-stature-related genes was performed for the probands. Variants detected by NGS were confirmed by Sanger sequencing and examined in family members. RESULTS: The probands presented with characteristic features of severe growth delay, poikiloderma mostly on the face, buttocks and extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction defects, small hands with hypoplasia of the middle phalanx (little finger) in one of the probands, epicanthus, hypertelorism, and dental abnormalities. In addition, novel auricle features and other rare facial features, including narrow palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four novel RECQL4 variants were identified, including three pathogenic frameshift variants, c.1724_1725delAC, p.His575fs*7; c.2421dupT, p.Asp808*; c.1770_1807del, p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser. CONCLUSION: Our study expands the mutational spectrum of RECQL4 gene and reveals novel phenotypes observed in Chinese RTS patients.

Poikiloderma with neutropenia: report of three cases including one with calcinosis cutis.

Poikiloderma with neutropenia (PN), Clericuzio type (OMIM #604173) is a new, unique genodermatosis first described by Clericuzio et al (Am J Med Genet A, 2011, 155, 337) in Navajo Indian population. This disease is characterized by poikiloderma that usually develops in the first year of life and is associated with nail abnormality, palmoplantar hyperkeratosis, chronic neutropenia, and recurrent infections. The rash typically starts from the extremities and spreads centripetally to involve the trunk, face, and ears. Recently, a homozygous mutation in the C16orf57 gene on chromosome 16q13 was identified as a strong candidate as the gene responsible for PN. We report three cases of PN whose clinical presentations, laboratory investigations, and C16orf57 mutation support the diagnosis of PN. One child has developed multiple painful calcinosis cutis lesions. Early-onset poikiloderma should prompt a complete blood count as a screening test.