Aberrant splicing due to a novel RPS7 variant causes Diamond-Blackfan Anemia associated with spontaneous remission and m
- PDF / 1,911,111 Bytes
- 6 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 159 Views
CASE REPORT
Aberrant splicing due to a novel RPS7 variant causes Diamond‑Blackfan Anemia associated with spontaneous remission and meningocele Talia Akram1,2 · Ambrin Fatima2 · Joakim Klar2 · Jan Hoeber2 · Muhammad Zakaria3 · Muhammad Tariq1 · Shahid M. Baig1 · Jens Schuster2 · Niklas Dahl2 Received: 16 January 2020 / Revised: 30 June 2020 / Accepted: 14 July 2020 © Japanese Society of Hematology 2020
Abstract Diamond-Blackfan Anemia (DBA) is a congenital pure red cell aplasia caused by heterozygous variants in ribosomal protein genes. The hematological features associated with DBA are highly variable and non-hematological abnormalities are common. We report herein on an affected mother and her daughter presenting with transfusion-dependent anemia. The mother showed mild physical abnormalities and entered spontaneous remission at age 13 years. Her daughter was born with occipital meningocele. Exome sequencing of DNA from the mother revealed a heterozygous novel splice site variant (NM_001011.4:c.508-3T > G) in the Ribosomal Protein S7 gene (RPS7) inherited by the daughter. Functional analysis of the RPS7 variant expressed from a mini-gene construct revealed that the exon 7 acceptor splice site was replaced by a cryptic splice resulting in a transcript missing 64 bp of exon 7 (p.Val170Serfs*8). Our study confirms a pathogenic effect of a novel RPS7 variant in DBA associated with spontaneous remission in the mother and meningocele in her daughter, thus adding to the genotype–phenotype correlations in DBA. Keywords Diamond-Blackfan Anemia (DBA) · Meningocele · Spontaneous remission · RPS7 gene variant · In vitro splicing
Introduction Diamond-Blackfan Anemia (DBA; OMIM: 105650) is a rare congenital bone marrow failure syndrome with a reported incidence 5–10 per 1000,000 live births [1]. The most prominent clinical features in DBA are chronic macrocyticnormochromic anemia, reticulocytopenia and a differentiation block confined to the erythropoietic lineage [1, 2]. Furthermore, almost 50% of cases with DBA present with various non-hematological features such as developmental * Niklas Dahl [email protected] 1
Human Molecular Genetics Laboratory, National Institute for Biotechnology and Genetic Engineering (NIBGE-C)PIEAS, Faisalabad, Pakistan
2
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, BMC Box 815, Uppsala, Sweden
3
Center for Human Genetics, Hazara University, Mansehra, Pakistan
delay, craniofacial and upper limb malformations, heart and urinary system deformities [2, 3]. Blood transfusions and corticosteroid therapy are the standard treatments for patients independent of the hematological status and age at presentation. Spontaneous remissions occur in 20% of cases and irrespective of prior treatments [4]. After the original finding on ribosomal protein gene RPS19 in 25% of cases with DBA [5], heterozygous gene variants have been identified in altogether 31 genes encoding proteins of either the small ribosomal subunit or the large ribosomal s
Data Loading...
