Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency |
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| Authors: | E Quintana L Gort C Busquets A Navarro‐Sastre W Lissens S Moliner M Lluch MA Vilaseca L De Meirleir A Ribes P Briones PDH Working Group |
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| Affiliation: | 1. Institut de Bioquímica Clínica, Servei de Bioquímica i Genètica Molecular, Hospital Clínic, Barcelona, Spain;2. CIBER de Enfermedades Raras (CIBERER), Barcelona, Spain;3. UZ Brussel, Vrije Universiteit Brussel, Belgium;4. Servei de Bioquímica, Hospital Sant Joan de Déu, Barcelona, Spain;5. PDH Working Group includes physicians who provided patients' samples and clinical data: JL Tarazona (Hospital General d’Alacant), Mercé Pineda, MA García‐Cazorla, P Poo (Hospital Sant Joan de Deu, Barcelona), Navarro‐Morón (Hospital Puerta del Mar, Cadiz), MT García‐Silva, E Martín (Hospital 12 de Octubre, Madrid), M Aritmendi (Hospital General Gregorio Mara?ón, Madrid), M Martinez‐Pardo (Hospital Ramón y Cajal, Madrid), A García‐Alix (Hospital La Paz, Madrid), R Domingo (Hospital Virgen de la Arrixaca, Murcia), MA Ruiz (Hospital Son Dureta, Palma de Mallorca), E Lewis, CF Moura de Souza (Porto Alegre–Brasil), ME Yoldi (Hospital Virgen del Camino, Pamplona), MR Rodrigues (IG Jacinto Magalhaes, Porto, Portugal), A Martinez–Carrascal (Hospital de Requena), M Castro‐Gago (Hospital Clínico, Santiago de Compostela), JI Mu?oz, C Martínez‐Costa (Hospital Clínico, Valencia). |
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| Abstract: | ![]()
Quintana E, Gort L, Busquets C, Navarro‐Sastre A, Lissens W, Moliner S, Lluch M, Vilaseca MA, De Meirleir L, Ribes A, Briones P, PDH Working Group. Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency. We screened for PDHA1 mutations in 40 patients with biochemically demonstrated PDHc deficiency or strong clinical suspicion, and found changes with probable pathological significance in 20. Five patients presented new mutations: p.A169V, c.932_938del, c.1143_1144 ins24, c.1146_1159dup and c.510‐30G> A, this latter is a new undescribed cause of exon 6 skipping. Another four mutations have been found, and previously reported, in our patients: p.H113D, p.P172L, p.Y243del and p.Y369Q. Eleven patients presented seven known mutations: p.R127Q, p.I166I, p.A198T, p.R263G, p.R302C, p.R378C and c.1142_1145dup. The latter three were found in more than one unrelated patient: p.R302C was detected in a heterozygous girl and a mosaic male, p.R378C in two males and finally, c.1142_1145dup in three females; only one in 20 mothers was found to be a carrier (p.R263G). Apart from those 20 patients, the only alteration detected in one girl with clear PDHc and PDH‐E1 deficiency was the silent change c.396A> C (p.R132R), and other eight PDHc deficient patients carry combinations of known infrequent polymorphisms that are overrepresented among our 20 unsolved patients. The importance of these changes on PDH activity is unclear. Investigations in the other PDHc genes are in course in order to elucidate the genetic defect in the unresolved patients. |
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| Keywords: | mosaicism mutation analysis PDHA1 gene PDH activity PDHc deficiency |
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