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Novel mutations causing biotinidase deficiency in individuals identified by the newborn screening program in Minas Gerais, Brazil
Author(s) -
Carvalho Nara O.,
Castillo Dora M.,
Januário José N.,
Starling Ana L. P.,
Arantes Rodrigo R.,
Norton Rocksane C.,
Viana Marcos B.
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61137
Subject(s) - biotinidase deficiency , missense mutation , newborn screening , mutation , compound heterozygosity , exon , genetics , genotype , biology , gene , heterozygote advantage , phenotype , endocrinology , medicine , microbiology and biotechnology
Biotinidase deficiency is an autosomal recessive inherited metabolic disorder caused by mutations in the BTD gene. Clinical manifestations can be treated and effectively prevented with pharmacological doses of biotin. Nine novel mutations in BTD are reported in 14 children diagnosed by the newborn screening program in Minas Gerais, Brazil, from June 2013 to December 2017. Serum BTD enzyme activity was determined for all cases and some parents. Two of the mutations are deletions and seven missense mutations located in the exonic region of the BTD gene, mostly in exon 4. Two newborns were profoundly biotinidase‐deficient (one homozygous p.A534V [c.1601C > T] and another, double heterozygous for a novel mutation p.R211S [c.631C > A] co‐inherited with an already described mutation p.T532 M [c.1595C > T]). Two mutations were associated with a partial deficiency of biotinidase (p.F361 V [c.1081 T > G] in two homozygous children, and p.S311 T [c.932G > C] in a compound heterozygous child who co‐inherited a known severe mutation p.Y438X [c.1314 T > A]). The remaining five mutations were found in compound heterozygous children. Hence, a definitive conclusion about the degree of biotinidase deficiency is not possible yet. These results emphasize the importance of sequencing the BTD gene as an important tool to gain a better understanding of the correlation between biochemical phenotype and genotype.