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

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Abstract

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
JournalGene
Volume844
DOIs
Publication statusPublished - 30 Nov 2022

Bibliographical note

Funding Information:
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Asmahan T. Abdalla reports financial support was provided by European Society for Pediatric Endocrinology.

Publisher Copyright:
© 2022 Elsevier B.V.

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