The Biotinidase Gene Variants Registry: A Paradigm Public Database

Abstract

The BTD gene codes for production of biotinidase, the enzyme responsible for helping the body reuse and recycle the biotin found in foods. Biotinidase deficiency is an autosomal recessively inherited disorder resulting in the inability to recycle the vitamin biotin and affects approximately 1 in 60,000 newborns. If untreated, the depletion of intracellular biotin leads to impaired activities of the biotin-dependent carboxylases and can result in cutaneous and neurological abnormalities in individuals with the disorder. Mutations in the biotinidase gene (BTD) alter enzymatic function. To date, more than 165 mutations in BTD have been reported. Our group has developed a database that characterizes the known mutations and sequence variants in BTD. (http://arup.utah.edu/database/BTD/BTD_welcome.php). All sequence variants have been verified for their positions within the BTD gene and designated according to standard nomenclature suggested by Human Genome Variation Society (HGVS). In addition, we describe the change in the protein, indicate whether the variant is a known or likely mutation vs. a benign polymorphism, and include the reference that first described the alteration. We also indicate whether the alteration is known to be clinically pathological based on an observation of a known symptomatic individual or predicted to be pathological based on enzymatic activity or putative disruption of the protein structure. We incorporated the published phenotype to help establish genotype-phenotype correlations and facilitate this process for those performing mutation analysis and/or interpreting results. Other features of this database include disease information, relevant links about biotinidase deficiency, reference sequences, ability to query by various criteria, and the process for submitting novel variations. This database is free to the public and will be updated quarterly. This database is a paradigm for formulating databases for other inherited metabolic disorders.

First contiguous gene deletion causing biotinidase deficiency: The enzyme deficiency in three Sri Lankan children

“…Mutation analysis revealed that this boy was homozygous for c.98_104 del7insTCC; p.C33FfsX36 in the BTD gene [6]. This mutation is a relative common mutation in Western European countries and results in a frameshift and the synthesis of a truncated, inactive enzyme protein causing profound biotinidase deficiency.…”

Clinical, Biochemical and Outcome Profile of Biotinidase Deficient Patients from Tertiary Centre in Northern India

“…Mutation in BTD gene leads to altered enzyme activity. There are nearly 165 mutations have been reported in literature so far [16]. We could not genotype our cases as this facility was not available at our centre.…”

Biochemical Hyperthyroidism in a Newborn Baby Caused by Assay Interaction from Biotin Intake

“…Biotinidase deficiency is an autosomal recessive disease, and more than 165 different mutations have been identified [8]. In the present case, the brother of the newborn was homozygotic for biotinidase deficiency and harboring two different mutations, one from each parent as both parents were heterozygotic carriers of the disease.…”