Btd-KO Mouse

Btd, short for biotinidase, is the sole enzyme capable of cleaving biocytin, a product from the proteolytic digestion of holocarboxylases. This process is crucial for the recycling of free biotin, which is essential for biotin-dependent carboxylase functions. It is involved in maintaining normal neurological and cutaneous functions, and its deficiency can lead to autosomal recessive disorders affecting these systems [1].

Mutations in the BTD gene cause biotinidase deficiency. Profound BTD deficiency (less than 10% mean normal activity in serum) has been associated with 61 mutations in three of the four exons and one mutation in an intron. For example, mutations 98-104del7ins3 and R538C were present in 52% of alleles in symptomatic patients, while A755G, Q456H, and 511 G>A; 1330G>C (double mutation) accounted for 52% of alleles detected by newborn screening in the US [1]. Different mutations have also been found in Turkish, Saudi Arabian, Japanese, Pakistani, and Chinese children with profound BTD deficiency [1,3,4]. Partial BTD deficiency (10-30% of mean normal serum activity) is often caused by the 1330G>C mutation resulting in D444H on one allele, combined with a profound-deficiency-causing mutation on the other allele [1]. In vitro studies on BTD gene variants in Brazilian individuals showed that some variants like p.Leu40Pro, p.Cys160Tyr, and p.Leu446Pro were deleterious, p.Asn489Ser was related to a mild biochemical phenotype, and p.Asp222Asn was likely not deleterious, while p.Asp444His had variable activity [2].

In conclusion, Btd is essential for biotin recycling and normal carboxylase function, with its deficiency leading to various neurological and cutaneous abnormalities. Studies on gene mutations in BTD-deficient patients across different ethnic groups have provided insights into the genetic basis of biotinidase deficiency, which is crucial for early diagnosis, genetic counseling, and management of this autosomal recessive disorder.

References:

1. Hymes, J, Stanley, C M, Wolf, B. . Mutations in BTD causing biotinidase deficiency. In Human mutation, 18, 375-81. doi:. https://pubmed.ncbi.nlm.nih.gov/11668630/

2. Borsatto, Taciane, Sperb-Ludwig, Fernanda, Blom, Henk J, Schwartz, Ida V D. 2019. Effect of BTD gene variants on in vitro biotinidase activity. In Molecular genetics and metabolism, 127, 361-367. doi:10.1016/j.ymgme.2019.07.006. https://pubmed.ncbi.nlm.nih.gov/31337602/

3. Moatter, Tariq, Ahmed, Sibtain, Majid, Hafsa, Bilal, Muhammad, Khan, Aysha Habib. 2023. Sequence variants in the BTD underlying biotinidase deficiency in families of Pakistani origin. In The journal of gene medicine, 26, e3597. doi:10.1002/jgm.3597. https://pubmed.ncbi.nlm.nih.gov/37751899/

4. Geng, Jia, Sun, Yi, Zhao, Yi, Lu, Yu, Yuan, Huijun. 2021. Two novel BTD mutations causing profound biotinidase deficiency in a Chinese patient. In Molecular genetics & genomic medicine, 9, e1591. doi:10.1002/mgg3.1591. https://pubmed.ncbi.nlm.nih.gov/33452876/