Vitamin D-binding protein deficiency: an underrecognized Mendelian disorder of vitamin D metabolism.

IF 3.8 2区生物学 Q2 GENETICS & HEREDITY

Human Genetics Pub Date : 2024-02-01 Epub Date: 2024-01-24 DOI:10.1007/s00439-023-02632-3

Zainab Al Masseri, Mashael Alqahtani, Eman Almoshawer, Fowzan S Alkuraya

引用次数: 0

Abstract

Vitamin D-binding protein (VDBP) deficiency is a recently discovered apparently benign biochemical disorder that can masquerade as treatment-resistant vitamin D deficiency and is likely underrecognized. We present the case of a child with persistently low 25OH vitamin D levels despite replacement therapy. Exome sequencing revealed a novel homozygous nonsense variant in the GC gene, leading to undetectable levels of VDBP. Interestingly, exome sequencing also revealed a homozygous loss-of-function variant in ZNF142, which likely explains the additional clinical features of recurrent febrile convulsions and global developmental delay. Our findings corroborate the two previously reported patients with autosomal recessive VDBP deficiency caused by biallelic GC variants and emphasize the importance of measuring VDBP levels in cases of apparent vitamin D deficiency that is treatment-resistant. We also urge caution in concluding "atypical" presentations without careful investigation of a potential dual molecular diagnosis.

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维生素 D 结合蛋白缺乏症：一种未得到充分认识的孟德尔维生素 D 代谢紊乱。

维生素 D 结合蛋白（VDBP）缺乏症是最近发现的一种表面上看似良性的生化疾病，可伪装成耐药性维生素 D 缺乏症，而且很可能未得到充分认识。我们介绍了一例尽管接受了替代疗法，但 25OH 维生素 D 水平持续偏低的儿童病例。外显子组测序发现了 GC 基因中的一个新型同源无义变异，导致检测不到 VDBP 水平。有趣的是，外显子组测序还发现了ZNF142基因中的一个同源功能缺失变体，这很可能是该患者反复发热惊厥和全面发育迟缓等额外临床特征的原因。我们的研究结果证实了之前报道的两名由双倍性 GC 变异引起的常染色体隐性 VDBP 缺乏症患者，并强调了在出现明显的维生素 D 缺乏症且耐药的病例中测量 VDBP 水平的重要性。我们还呼吁，在没有仔细调查潜在的双重分子诊断之前，谨慎得出 "非典型 "的结论。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genetics 生物-遗传学

CiteScore

10.80

自引率

3.80%

发文量

审稿时长

1 months

期刊介绍： Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.