Boczek Nicole J, Kruisselbrink Teresa, Cousin Margot A, Blackburn Patrick R, Klee Eric W, Gavrilova Ralitza H, Lanpher Brendan C
Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota.
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
Am J Med Genet A. 2017 May;173(5):1328-1333. doi: 10.1002/ajmg.a.38113. Epub 2017 Mar 21.
STAR syndrome is a rare X-linked dominant disorder characterized by toe Syndactyly, Telecanthus, Anogenital malformations, and Renal malformations, and is caused by loss-of-function variants in FAM58A. Our proband presented with the hallmark features of STAR syndrome, as well as some additional less typical features including tethered cord and hearing loss. The proband's mother and maternal half-sister had similar clinical histories, but had variability in phenotypic severity. Clinical whole exome sequencing revealed a novel pathogenic nonsense variant, c.651G>A (p.Trp217X; NM_152274), in FAM58A in the proband, mother, and maternal half-sister. This pedigree represents the 11-13th patients described with STAR syndrome and the third instance of familial inheritance. To our knowledge, this is the first occurrence of a nonsense variant in FAM58A described in individuals with STAR syndrome and the phenotype in this pedigree suggests that tethered cord and hearing loss are features of STAR syndrome.
STAR综合征是一种罕见的X连锁显性疾病，其特征为足趾并指、眼距增宽、肛门生殖器畸形和肾脏畸形，由FAM58A功能丧失变异引起。我们的先证者表现出STAR综合征的标志性特征，以及一些其他不太典型的特征，包括脊髓栓系和听力丧失。先证者的母亲和同父异母的姐姐有相似的临床病史，但表型严重程度存在差异。临床全外显子测序在先证者、母亲和同父异母的姐姐的FAM58A中发现了一个新的致病性无义变异，即c.651G>A（p.Trp217X；NM_152274）。这个家系代表了第11 - 13例被描述为STAR综合征的患者以及家族遗传的第三个实例。据我们所知，这是首次在STAR综合征患者中描述FAM58A中的无义变异，并且这个家系中的表型表明脊髓栓系和听力丧失是STAR综合征的特征。
