Departamento de Genética, Facultad de Medicina y Hospital Universitario José E González, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México.
Am J Med Genet A. 2013 Feb;161A(2):237-43. doi: 10.1002/ajmg.a.35743. Epub 2013 Jan 10.
The family observed in this study included affected males and asymptomatic females. The patients shared specific digital abnormalities including postaxial polydactyly, cutaneous syndactyly, and brachydactyly. In addition, the patients exhibited mild-to-moderate intellectual disability and short stature coupled with microbrachycephaly, scoliosis, and cerebellar and renal hypoplasia. No chromosomal alterations or copy number variations were found in the index case. The genetic linkage analysis, which focused on the X chromosome, and the haplotype analysis detected a ~15.74 Mb candidate region located at Xp11.4-p11.21 with a LOD score of 4.8. Additionally, half of the mothers showed skewed X-inactivation, while the other mothers exhibited random inactivation patterns. The candidate region includes 28 protein-encoding genes that have not yet been implicated in human disorders. We speculate that the observed phenotype is compatible with a monogenic disorder in which the mutant gene plays a significant role during embryonic development. Based on the patients' clinical features, image studies, pedigree, chromosome location, and X-inactivation studies in the mothers, we propose that this family has a novel, specific syndrome with an X-linked recessive mode of inheritance.
本研究观察到的家系包括患病男性和无症状女性。这些患者具有特定的数字异常，包括轴后多指、皮肤并指和短指。此外，患者还表现出轻度至中度智力障碍和身材矮小，伴有小头畸形、脊柱侧凸、小脑和肾脏发育不良。在索引病例中未发现染色体改变或拷贝数变异。针对 X 染色体的遗传连锁分析和单倍型分析检测到一个位于 Xp11.4-p11.21 的约 15.74Mb 候选区域，其 LOD 得分为 4.8。此外，一半的母亲表现出偏性 X 染色体失活，而其他母亲则表现出随机失活模式。候选区域包括 28 个尚未涉及人类疾病的蛋白编码基因。我们推测观察到的表型与一种单基因疾病相符，其中突变基因在胚胎发育过程中发挥重要作用。基于患者的临床特征、影像学研究、家系、染色体定位以及母亲的 X 染色体失活研究，我们提出该家系具有一种新的、特定的 X 连锁隐性遗传综合征。
