Mutations in PCYT1A Cause Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy

Autor(es):Mostrar menos -

Yamamoto, Guilherme L. ^{[1, 2]} ; Baratela, Wagner A. R. ^[1] ; Almeida, Tatiana F. ^[1] ; Lazar, Monize ^[2] ; Afonso, Clara L. ^[3] ; Oyamada, Maria K. ^[3] ; Suzuki, Lisa ^[4] ; Oliveira, Luiz A. N. ^[4] ; Ramos, Ester S. ^[5] ; Kim, Chong A. ^[1] ; Passos-Bueno, Maria Rita ^[2] ; Bertola, Debora R. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Unidade Genet, Inst Crianca, BR-05403000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biociencias, Ctr Estudos Genoma Humano, BR-05508090 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Oftalmol, BR-05403000 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Radiol, Inst Crianca, BR-05403000 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, BR-14049900 Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: American Journal of Human Genetics; v. 94, n. 1, p. 113-119, JAN 2 2014.
• Citações Web of Science: 19

Resumo

Spondylometaphyseal dysplasia with cone-rod dystrophy is a rare autosomal-recessive disorder characterized by severe short stature, progressive lower-limb bowing, flattened vertebral bodies, metaphyseal involvement, and visual impairment caused by cone-rod dystrophy. Whole-exome sequencing of four individuals affected by this disorder from two Brazilian families identified two previously unreported homozygous mutations in PCYT1A. This gene encodes the alpha isoform of the phosphate cytidylyltransferase 1 choline enzyme, which is responsible for converting phosphocholine into cytidine diphosphate-choline, a key intermediate step in the phosphatidylcholine biosynthesis pathway. A different enzymatic defect in this pathway has been previously associated with a muscular dystrophy with mitochondrial structural abnormalities that does not have cartilage and/or bone or retinal involvement. Thus, the deregulation of the phosphatidylcholine pathway may play a role in multiple genetic diseases in humans, and further studies are necessary to uncover its precise pathogenic mechanisms and the entirety of its phenotypic spectrum. (AU)

• Processo FAPESP: 98/14254-2 - Centro de Estudos do Genoma Humano
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs