title: Biotinidase deficiency due to a de novo mutation or gonadal mosaicism in a first child.
abstract: Biotinidase deficiency (BD), which is caused by BTD genetic lesions, if untreated, can result in neurological and cutaneous manifestations. Biotin supplementation can improve or prevent symptoms. We herewith present a family, which we studied at biochemical and molecular level, after identifying the proband through a newborn screening programme. BTD gene molecular analysis showed the proband to be compound heterozygous for the c.1330G>C p.(Asp444His) mild known variant, and for the c.1475 C>T p.(Thr492Ile) new variant. Bioinformatic analysis allowed us to confirm the pathogenic role of the newly identified variant. The proband's father, who exhibited low biotinidase (BTD) enzyme activity, was homozygous for the mild variant, whereas the proband's mother, who exhibited borderline BTD values, the BTD mutation carrier status could not be detected. This is the first description of a patient with BD harbouring a variant whose origin is either de novo or the consequence of gonadal mosaicism. BTD molecular analysis and bioinformatic tools for the evaluation of pathogenicity of newly identified variants are necessary for diagnostic purposes (i.e., clarifying borderline enzyme assays and the carrier status of parents), and for genetic counselling.
authors: Molecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy; Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Italy.
authors: Rodolfo
authors: R
authors: Tonin
authors: Molecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy.
authors: Anna
authors: A
authors: Caciotti
authors: Newborn Screening Biochemistry and Pharmacology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy.
authors: Silvia
authors: S
authors: Funghini
authors: Newborn Screening Biochemistry and Pharmacology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy.
authors: Giancarlo
authors: G
authors: la Marca
authors: Metabolic and Muscular Unit, A. Meyer Children's Hospital, Florence, Italy.
authors: Elisabetta
authors: E
authors: Pasquini
authors: Buck Institute for Research on Aging, Novato, CA, USA.
authors: Erica
authors: E
authors: Cayton
authors: Buck Institute for Research on Aging, Novato, CA, USA.
authors: Sean D
authors: SD
authors: Mooney
authors: Molecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy; Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Italy.
authors: Renzo
authors: R
authors: Guerrini
authors: Molecular and Cell Biology Laboratory, Paediatric Neurology Unit and Laboratories, Neuroscience Department, A. Meyer Children's Hospital, Florence, Italy; Department of Neurosciences, Psychology, Pharmacology and Child Health, University of Florence, Italy. Electronic address: a.morrone@meyer.it.
authors: Amelia
authors: A
authors: Morrone
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D043523:Biotinidase / Q000235:genetics*; D028921:Biotinidase Deficiency / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005817:Genetic Counseling; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D015997:Neonatal Screening; D010290:Parents
chemical_list: D043523:Biotinidase
keywords: BTD; Bioinformatic prediction tools; Biotinidase deficiency; De novo mutation; Unusual biochemical–molecular correlation