Santos syndrome is caused by mutation in the WNT7A gene

Autor(es)

Alves, Leandro U. ^[1] ; Santos, Silvana ^[2] ; Musso, Camila M. ^[1] ; Ezquina, Suzana A. M. ^[1] ; Opitz, John M. ^[3] ; Kok, Fernando ^{[4, 5]} ; Otto, Paulo A. ^[1] ; Mingroni-Netto, Regina C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, Rua Matao 277, BR-05508900 Sao Paulo, SP - Brazil

^[2] Univ Estadual Paraiba, Dept Biol, Campina Grande, PB - Brazil

^[3] Univ Utah, Hlth Sci Ctr, Pediat Div Med Genet, Human Genet, Pathol, Obstet & Gynecol, Salt Lake City, UT - USA

^[4] Univ Sao Paulo, Fac Med, Dept Neurol, Sao Paulo, SP - Brazil

^[5] Univ Sao Paulo, Fac Med, Hosp Clin, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF HUMAN GENETICS; v. 62, n. 12, p. 1073-1078, DEC 2017.
• Citações Web of Science: 4

Resumo

We have recently described a family with a condition (Santos syndrome (SS; MIM 613005)) characterized by fibular agenesis/ hypoplasia, hypoplastic femora and grossly malformed/deformed clubfeet with severe oligodactyly, ungual hypoplasia/anonychia, sometimes associated with mild brachydactyly and occasional pre-axial polydactyly. Autosomal dominant inheritance with incomplete penetrance was suggested, but autosomal recessive inheritance could not be ruled out, due to the high frequency of consanguineous matings in the region where the family lived. This report deals with linkage studies and exome sequencing, disclosing a novel variant in WNT7A, c. 934G4A (p. Gly312Ser), as the cause of this syndrome. This variant was present in homozygous state in five individuals typically affected by the SS syndrome, and in heterozygous state in the son of one affected homozygous individual. The heterozygous boy presented only unilateral complex polysyndactyly and we hypothesize that he either presents a distinct defect or that his phenotype results from a rare, mild clinical manifestation of the variant in heterozygous state. Variants in WNT7A are known to cause at least two other limb defect disorders, the syndromes of Fuhrmann and Al-Awadi/ Raas-Rothschild. Despite their variable degree of expressivity and overlap, the three related conditions can be differentiated phenotypically in most instances. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs