Seventeen novel mutations that cause profound biotinidase deficiency

Wolf, Barry; Jensen, Kevin P.; Hüner, G.; Demirkol, Mübeccel; Baykal, T.; Divry, P.; Rolland, Marie-Odile; Pérez‐Cerdá, Celia; Ugarte, Magdalena; Straussberg, Rachel; Basel‐Vanagaite, Lina; Baumgartner, E. R.; Suormala, Terttu; Scholl, Sabine; Das, Anibh M.; Schweitzer, Simone; Pronicka, Ewa; Sykut-Cegielska, Jolanta

doi:10.1016/s1096-7192(02)00149-x

Cited by 32 publications

(17 citation statements)

References 11 publications

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“…To raise these antibodies, the following peptides were custom-synthesized by the University of Virginia Biomolecular Research Facility (Charlottesville, VA, USA): (a) N 1)13 bioK4, ARTK(biotin)QTARKSTGGC (amino acids 1-13 in histone H3); (b) N 1)13 bioK9, ARTK-QTARK(biotin)STGGC (amino acids 1-13); and (c) N 13)25 bioK18, GKAPRK(biotin)QLATKAAC (amino acids [13][14][15][16][17][18][19][20][21][22][23][24][25]. Peptide identities were confirmed by MS. Peptides were conjugated to keyhole limpet hemocyanin by utilizing the C-terminal cysteine [7]; these peptide conjugates were injected into white New Zealand rabbits, following NIH and USDA guidelines for animal care.…”

Section: Polyclonal Antibodiesmentioning

confidence: 99%

K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase

et al. 2005

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Histones are modified post‐translationally, e.g. by methylation of lysine and arginine residues, and by phosphorylation of serine residues. These modifications regulate processes such as gene expression, DNA repair, and mitosis and meiosis. Recently, evidence has been provided that histones are also modified by covalent binding of the vitamin biotin. The aims of this study were to identify biotinylation sites in histone H3, and to investigate the crosstalk among histone biotinylation, methylation and phosphorylation. Synthetic peptides based on the sequence of human histone H3 were used as substrates for enzymatic biotinylation by biotinidase; biotin in peptides was probed using streptavidin peroxidase. These studies provided evidence that K4, K9 and K18 in histone H3 are good targets for biotinylation; K14 and K23 are relatively poor targets. Antibodies were generated to histone H3, biotinylated either at K4, K9 or K18. These antibodies localized to nuclei in human placental cells in immunocytochemistry and immunoblotting experiments, suggesting that lysines in histone H3 are biotinylated in vivo. Dimethylation of R2, R8 and R17 increased biotinylation of K4, K9 and K18, respectively, by biotinidase; phosphorylation of S10 abolished biotinylation of K9. These observations are consistent with crosstalk between biotinylation of histones and other known modifications of histones. We speculate that this crosstalk provides a link to known roles for biotin in gene expression and cell proliferation.

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Section: Polyclonal Antibodiesmentioning

confidence: 99%

K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase

et al. 2005

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“…Nos. 1, 2, 17 have already been published in 2002, in the report by Wolf et al on seventeen novel mutations causing profound biotinidase deficiency [8].…”

Section: Resultsmentioning

confidence: 97%

Outcomes of oral biotin treatment in patients with biotinidase deficiency — Twenty years follow-up

Szymańska

Średzińska

Ługowska

et al. 2015

Molecular Genetics and Metabolism Reports

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IntroductionBiotinidase deficiency (BTD) is an inborn error of biotin metabolism inherited as an autosomal recessive trait. Due to the, biotinidase deficiency, biotin is not recycled. Individuals with BTD usually exhibit neurological and cutaneous abnormalities unless treated with biotin. Supplementation with biotin may either ameliorate or if early introduced even prevent symptoms when introduced presymptomatically.Patients and methodsSince 1991, 22 Polish patients from 19 families have been diagnosed with BTD. In 16 children the diagnosis had been suspected on the basis of clinical signs: skin lesions, hyperventilation, seizures, spasticity, and laboratory investigation (elevated lactate and metabolites on urine organic acids profile).The defect was enzymatically (serum biotinidase activity measurement) and genetically (tested for mutations in the BTD gene) confirmed afterwards. All patients were treated with biotin. Urine organic acids analysis (GC/MS) for 3-hydroxizovaleric acid was used for patients' monitoring. Neurological, audiological and ophthalmological evaluation has been conducted once a year.ResultsIn 5 symptomatic patients a progressive optic nerve atrophy had already been noted at the time of treatment initiation. In these patients sensorineural hearing loss has also been diagnosed despite biotin supplementation. Asymptomatic patients treated with biotin supplementation presented no signs or symptoms of BTD. Supplementation with biotin slows the progression of BTD in symptomatic patients, but does not reverse nerve atrophy. Nonetheless, introduction of the treatment with biotin during presymptomatic stage of the disease prevents the onset of symptoms including optic atrophy and hearing loss. Homozygosity for the p.Leu215Phe mutation in BTD gene seems to be frequent in patients from the North-Eastern region of Poland and is connected with the hearing loss.ConclusionSince the prognosis for individuals diagnosed with BTD is good, provided they are treated before symptoms occur, it is justified to add this metabolic disorder to the panel of conditions screened under the national newborn screening programme in Poland.

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“…With time, the European investigators above began to confirm that their patients with multiple carboxylase deficiency had biotinidase deficiency and proceeded to report their clinical and laboratory studies [37][38][39][40][41][42][43][44][45]. In fact, we collaborated and published with Regula and Terttu [46,47]. Almost all the individuals with late-onset multiple or combined carboxylase deficiency were shown to have biotinidase deficiency.…”

Section: Spreading the Word About Biotinidase Deficiencymentioning

confidence: 99%

The Further Adventures of Newborn Screening for Biotinidase Deficiency: Where It Is at and What We Still Need to Know

Wolf

2016

IJNS

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Abstract:Biotinidase deficiency is an inherited metabolic disorder that, if untreated, can result in neurological and cutaneous symptoms. If treated with the vitamin biotin, individuals with the disorder can markedly improve, but still may have some irreversible problems if therapy is delayed. If treated at birth, biotin therapy can prevent the development of symptoms as indicated by long-term outcomes. Therefore, the disorder readily meets the major criteria for newborn screening. Our laboratory has been instrumental in developing, piloting and establishing newborn screening for the disorder in the United States and in many countries. This review discusses some of the "behind-the-scenes" aspects of how we spread the word about the disorder and what we learned from over 30 years of newborn screening. We also discuss some of the controversies and issues about biotinidase deficiency that remain to be addressed. Based on the successful outcomes of older adolescents and adults with profound biotinidase deficiency identified by newborn screening, this is one of the best, if not the best, disorder for which to perform newborn screening. In summary, "If an individual has to have an inherited metabolic disorder, biotinidase deficiency is the one to have."

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Seventeen novel mutations that cause profound biotinidase deficiency

Cited by 32 publications

References 11 publications

K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase

K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase

Outcomes of oral biotin treatment in patients with biotinidase deficiency — Twenty years follow-up

The Further Adventures of Newborn Screening for Biotinidase Deficiency: Where It Is at and What We Still Need to Know

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