Mutations In BCS1L Gene Research Articles

Clinical and diagnostic characteristics of complex III mitopathy due to novel BCS1L gene mutation in a Saudi patient

BackgroundOf the many types of mitochondrial diseases, mutations affecting BCS1L gene are regarded as chief cause of the defective mitochondrial complex-III, affecting normal mitochondrial functioning, and leading to wide variety of phenotypes.Case presentationIn this case report we describe a novel genotype linked to a unique phenotype in a Saudi patient born of a consanguineous marriage. Detailed genetic analysis and whole genome sequencing identified a novel homozygous missense mutation in exon 5 c.712A > G (p.Ser328Gly) of the BCS1L gene, with predicted deleterious effects on the functioning AAA+-ATPase domain of the protein characterized by distinct clinical presentation associated with profound multisystem involvement, conductive hearing loss, absent external auditory canal, low posterior hair line, short neck, micro and retrognathia, over riding fingers, rocker bottom foot, small phallus with bilateral absent testis (empty scrotum) and intolerable lactic acidosis.ConclusionsA pathogenic effect of this novel BCS1L mutation was reflected in the patient with his failure to thrive and a complex clinical and metabolic phenotype.

Bjornstad综合征致病BCS1L基因的新发突变位点研究

Objective To identify gene mutations in the BCS1L gene in a patient with Bjornstad syndrome mainly manifesting as congenital pili torti and sensorineural hearing loss. Methods Clinical data were collected and DNA was extracted from the peripheral blood of the patient and her parents. All the exons and their flanking sequences of the BCS1L gene were amplified by PCR followed by Sanger sequencing, and the sequencing results were compared with the normal sequences. A few hairs were collected from the patient, and examined by the scanning electron microscope. Results There were two mutations in BCS1L gene in the patient, i.e., a heterozygous nonsense mutation in exon 4 and a heterozygous missense mutation in exon 8. The nonsense mutation in exon 4, which caused a change from CGA to TGA at position 144 and resulted in the substitution of arginine by termination codon (p.R144*) , was a novel mutation in the BCS1L gene causing Bjornstad syndrome, and had never been reported in the literature. The missense mutation in exon 8 led to a change from CGC to CAC at position 306 and resulted in the substitution of arginine by histidine (p.R306H) . The patient′s mother only carried a heterozygous mutation c.430 C>T (p.R144*) in exon 4 of the BCS1L gene, and her father only carried a heterozygous mutation c.917 G>A (p.R306H) in exon 8 of the BCS1L gene. Scanning electron microscopy showed that flats, grooves and longitudinal twisting irregularly appeared at intervals on the surface of hair shafts. Conclusions A novel mutation in the BCS1L gene, which causes a change from CGA to TGA at position 144 in the BCS1L gene and results in a premature termination codon, is firstly reported in a patient with Bjornstad syndrome, and the compound heterozygous mutations c.430 C>T and c.917 G>A in the BCS1L gene are associated with the clinical manifestations of the patient. Genetic analysis is helpful for the diagnosis of Bjornstad syndrome. Key words: Mitochondrial diseases; Genes, mitochondrial; DNA mutational analysis; Bjornstad syndrome; BCS1L gene

Severe renal tubulopathy in a newborn due to BCS1L gene mutation: Effects of different treatment modalities on the clinical course

Very early onset Toni–Debré–Fanconi Syndrome, a disorder of proximal renal tubules of the kidney which results in the increased urinary excretion of glucose, amino acids, uric acid, phosphate and bicarbonate, could be the manifestation of various inborn errors. Defects of oxidative phosphorylation are a heterogeneous group of disorders with various clinical presentations. Recently, patients with early liver failure, renal tubulopathy and encephalopathy due to the mutations in the BCS1L gene coding for a structural protein in mitochondrial complex III have been described.Ten-day-old female newborn was referred to our clinic because of intractable acidosis. Physical examination revealed severe hypotonia, and hepatomegaly. The laboratory examinations revealed lactic acidosis, increased blood alanine, alanine aminotransferase and aspartate aminotransferase levels, generalized aminoaciduria and glucosuria. The tubular reabsorption of phosphate was reduced. Because of multisystem involvement, mitochondrial disease was suspected and the mutational analysis of the BCS1L gene revealed homozygous P99L mutation. As the patient was unresponsive to bicarbonate replacement, oral dichloroacetate and peritoneal dialysis, continuous high dose intravenous sodium bicarbonate therapy with a dose up to 1.25mEq/kg/h was started. The patient got on well until the age of 9months when she died of sepsis.It was stressed that high dose intravenous continuous sodium bicarbonate therapy could be an alternative treatment option in patients with severe acidosis and renal tubulopathy resistant to dichloroacetate and peritoneal dialysis. Patients with BCS1L mutations should be considered in the differential diagnosis of severe tubulopathy in the newborn period.

BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency

The clinical presentation of a neonate with GRACILE-like syndrome, complex III deficiency and BCS1L mutations is discussed. This case is compared and contrasted with the original Finnish reports of GRACILE syndrome and other cases with a similar phenotype. This case confirms the pathogenicity of the BCS1L gene mutation c.166C>T, and provides support for the pathogenicity of a sequence variation, c.-588T>A, previously reported.

P4.60 Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation

P4.60 Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation

Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation

Mutations of the BCS1L gene are a recognised cause of isolated respiratory chain complex III deficiency and underlie several fatal, neonatal mitochondrial diseases. Here we describe a 20-year-old Kenyan woman who initially presented as a floppy infant but whose condition progressed during childhood and adolescence with increasing muscle weakness, focal motor seizures and optic atrophy. Muscle biopsy demonstrated complex III deficiency and the pathogenicity of a novel, homozygous BCS1L mutation was confirmed by yeast complementation studies. Our data indicate that BCS1L mutations can cause a variable, neurological course which is not always fatal in childhood.

37 Heterozygous mutations in BCS1L gene: A clinical case of Bjornstad syndrome

37 Heterozygous mutations in BCS1L gene: A clinical case of Bjornstad syndrome