Further Evidence for RFWD3 Gene Causing Fanconi Anemia Complementation Group W: Detailed Clinical Report of the Second Case in the Literature - PubMed (original) (raw)

Further Evidence for RFWD3 Gene Causing Fanconi Anemia Complementation Group W: Detailed Clinical Report of the Second Case in the Literature

Sinem Kocagil et al. Mol Syndromol. 2023 Dec.

Abstract

Introduction: Fanconi anemia (FA) is a heterogeneous genetic disorder that is characterized by progressive bone marrow failure, congenital malformations, predisposition to malignancy, and short stature. The RFWD3 gene was recently associated with FA complementation group W, and only 1 patient is reported in the literature so far.

Case presentation: Here, we report the second patient, a 10-year-old male, who has failure to thrive, central nervous system abnormalities, bilateral radial ray defects, urogenital anomalies, facial dysmorphism, and thrombocytopenia. The patient was suspected to have FA according to the aforementioned findings, and the homozygous c.1501C>T variant in the RFWD3 gene was detected by whole-exome sequencing. The diepoxybutane test and mitomycin C-induced peripheral blood cultures revealed 0.46 and 0.90 chromosomal breaks, respectively.

Conclusion: In this article, clinical findings of the second patient with FA complementation group W are discussed in detail, aiming to expand the clinical and molecular spectrums of the disease.

Keywords: Fanconi anemia complementation group W; RFWD3; Radial ray defects; Rare variant.

© 2023 S. Karger AG, Basel.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1.

Fig. 1.

Skeletal survey images of the patient. a Radial ray deformity of the left arm. b Short and hypoplastic ulna. c Eversion of right tibiotalar joint. d Superiorly dislocated hypoplastic femoral heads. e Dextroscoliosis of the cervical spine indicated with a white arrow.

Fig. 2.

Fig. 2.

Patient at 10 years of age. a Triangular face, esotropia of the left eye, wide and flat nasal ridge, microstomia, low set ears, radial ray deformities, and tibiotalar eversion of the right foot. b Microtia of the left ear and midface hypoplasia.

Fig. 3.

Fig. 3.

Genetic analysis of the patient and the parents. a Homozygous p.Arg501Cys variant in the RFWD3 gene detected in the patient. b MMC-induced cultures demonstrated chromosomal tri-, tetra-, and polyradial formations detected at the metaphase of the peripheral blood culture of the patient indicated with blue arrows. c Heterozygous p.Arg501Cys variant in the RFWD3 gene detected in the mother. d Heterozygous p.Arg501Cys variant in the RFWD3 gene detected in the father. e 3D modeling of the mutation residue Arg501 of the protein is shown with a red arrow.

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