临床表型个体Biallelic Birk-Landau-Perez综合症SLC30A9致病变种

背景和目标Birk-Landau-Perez biallelic致病变种引起的综合症是一种遗传疾病SLC30A9有一个复杂的运动障碍,发展回归,眼球运动的异常、肾功能损害。它曾被报告2家庭。我们描述的临床表型8进一步个人从4无关的家庭SLC30A9有关的疾病。

方法详细的临床表型出现后,1家庭进行了全基因组测序的研究(WGS)诊断WGS 1研究whole-exome测序和2。为致病性变异的利益进行评估使用计算机预测工具,同源建模、相关,测序的互补DNA(互补)拼接效果。

结果2无关的巴基斯坦血统的家庭(1血缘和1)相同的纯合子的错义变体SLC30A9(c。1253G>T, p.Gly418Val) was identified. Family 1 included 2 affected brothers, and family 2 one affected boy. In family 3, also consanguineous, there were 4 affected siblings homozygous for the variant c.1049delCAG, pAla350del. The fourth family was nonconsanguineous: the 1 affected individual was compound heterozygous for c.1083dup, p.Val362Cysfs*5, and c.1413A>G, p.Ser471=. Despite phenotypic variability between the 4 families, all affected patients manifested with a progressive hyperkinetic movement disorder, associated with oculomotor apraxia and ptosis. None had evidence of severe renal impairment. For the novel missense variant, the conformation of the loop domain and packing of transmembrane helices are likely to be disrupted based on structure modeling. Its presence in 2 unrelated Pakistani families suggests a possible founder variant. For the synonymous variant p.Ser471=, an effect on splicing was confirmed through cDNA analysis.

讨论致病性变异在SLC30A9导致进步的常染色体隐性神经综合症与一个复杂的运动过度的运动障碍有关。我们的报告强调了扩大疾病表型,从而表现为更大范围的严重程度比此前被公认。