title: Mutations in PCYT1A cause spondylometaphyseal dysplasia with cone-rod dystrophy.
abstract: 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.
authors.affiliation: Unidade de Genética, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil; Centro de Estudos do Genoma Humano, Instituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil. Electronic address: guilherme.yamamoto@usp.br.
authors.forename: Guilherme L
authors.initials: GL
authors.lastname: Yamamoto
authors.affiliation: Unidade de Genética, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Wagner A R
authors.initials: WA
authors.lastname: Baratela
authors.affiliation: Unidade de Genética, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Tatiana F
authors.initials: TF
authors.lastname: Almeida
authors.affiliation: Centro de Estudos do Genoma Humano, Instituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Monize
authors.initials: M
authors.lastname: Lazar
authors.affiliation: Departamento de Oftalmologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Clara L
authors.initials: CL
authors.lastname: Afonso
authors.affiliation: Departamento de Oftalmologia, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Oyamada
authors.affiliation: Departamento de Radiologia, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Lisa
authors.initials: L
authors.lastname: Suzuki
authors.affiliation: Departamento de Radiologia, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Luiz A N
authors.initials: LA
authors.lastname: Oliveira
authors.affiliation: Departamento de Genética, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Ribeirão Preto 14049-900, Brazil.
authors.forename: Ester S
authors.initials: ES
authors.lastname: Ramos
authors.affiliation: Unidade de Genética, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil.
authors.forename: Chong A
authors.initials: CA
authors.lastname: Kim
authors.affiliation: Centro de Estudos do Genoma Humano, Instituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Passos-Bueno
authors.affiliation: Unidade de Genética, Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-000, Brazil; Centro de Estudos do Genoma Humano, Instituto de Biociências da Universidade de São Paulo, São Paulo 05508-090, Brazil.
authors.forename: Débora R
authors.initials: DR
authors.lastname: Bertola
mesh_terms: D000293:Adolescent; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D019916:Choline-Phosphate Cytidylyltransferase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009885:Ophthalmology / Q000379:methods; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D019916:Choline-Phosphate Cytidylyltransferase; C517213:PCYT1A protein, human