Clinical presentation and molecular genetic analysis of a Sudanese family with a novel mutation in the CYP2R1 gene

Asmahan T. Abdalla, Marijke Koedam, Sten L. S. Drop, Annemieke M. Boot, Muhamed A. Abdullah, Bram C. J. van der Eerden*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The aim of this study was to identify the genetic basis of two female siblings -born to consanguineous Sudanese parents -diagnosed clinically as having the rare condition of 25-hydroxylase deficiency (vitamin D-dependent rickets type 1B). The initial diagnosis was established based on clinical data, laboratory and radiological findings retrospectively. Primers for all exons (5) of human CYP2R1 (NM_024514) were generated followed by Sanger sequencing on exons 1-5 for both girls and their parents. Homozygosity for a point mutation (c.85C > T) was detected, leading to a nonsynonymous variant at position 29 in exon 1, resulting in a premature stop codon (p. Q29X). This is a previously unknown variant that leads to a severely truncated protein and predicted to be among the 0.1 % most deleterious genomic variants(CADD score 36). To our knowledge, this family represents the first case series from Sudan with a confirmed CYP2R1 gene mutation and the 6th world-wide. With the lack of genetic facilities, diagnosis should be suspected by the persistently low 25 hydroxyvitamin D level in spite of proper treatment and after ruling out liver disease and malabsorption. Patients in this case series showed healing of rickets when treated with high doses of 1,25-dihydroxyvitamin D3 (1,25(OH)D3; calcitriol) and oral calcium.

Original languageEnglish
Article number146809
Number of pages5
Publication statusPublished - 30-Nov-2022


  • Hereditary rickets
  • 25 OH vitamin D deficiency
  • Vitamin D-dependent rickets type 1b
  • Sanger sequencing

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