A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly.

Détails

ID Serval
serval:BIB_C42E286CF071
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly.
Périodique
European journal of pediatrics
Auteur(s)
Jackson C.B., Bauer M.F., Schaller A., Kotzaeridou U., Ferrarini A., Hahn D., Chehade H., Barbey F., Tran C., Gallati S., Haeberli A., Eggimann S., Bonafé L., Nuoffer J.M.
ISSN
1432-1076 (Electronic)
ISSN-L
0340-6199
Statut éditorial
Publié
Date de publication
04/2016
Peer-reviewed
Oui
Volume
175
Numéro
4
Pages
517-525
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article
Publication Status: ppublish
Résumé
We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood.
Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period.
• Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

Mots-clé
Acidosis, Lactic/genetics, Adolescent, Adult, Blotting, Western, Cholestasis/genetics, Deafness/genetics, Diagnosis, Differential, Electron Transport Complex III/deficiency, Electron Transport Complex III/genetics, Electrophoresis, Polyacrylamide Gel, Fanconi Syndrome/etiology, Fanconi Syndrome/genetics, Female, Fetal Growth Retardation/genetics, Growth Disorders/genetics, Hemosiderosis/genetics, Homozygote, Humans, Infant, Newborn, Intellectual Disability/genetics, Male, Metabolism, Inborn Errors/genetics, Microcephaly/genetics, Mitochondrial Diseases/congenital, Mitochondrial Diseases/genetics, Mutation, Missense, Renal Aminoacidurias/genetics
Pubmed
Création de la notice
26/04/2016 17:23
Dernière modification de la notice
03/03/2018 21:13
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