我们描述了一个纯粹的零星案例,串联,间质染色体4q复制,ARR[hg19]4q28.1q32.3(127,008,069-165,250,477)x3在怀孕36周出生的男孩。他出现了小头畸形(头围<1百分位数),身材矮小(身高<第二百分位数)和体重增加不良(体重<第三百分位数)。尿道超声检查后也发现了尿道下裂和马蹄形肾脏。生化分析显示生长激素和甲状腺激素水平正常。虽然总体和精细运动技能的发展与他的年龄一致,观察到语音延迟。该患者增加了一组30多例具有共同和不同表型表现的纯4q串联重复。使用对先前病例研究的回顾性分析以及对重复区域的当前病例和生物信息学分析,我们推断了患者中一些主要表型的最可能的剂量敏感基因.计算每个基因和表型的阳性预测值(PPV),并通过比较先前报道的具有基因重复和相关表型的患者与具有基因重复但不受影响的患者而得出。因此,生长迟缓表型可能与NAA15复制有关,语音延迟与GRIA2和小头畸形与PLK4重复。功能研究将有助于确认观察结果并阐明机制。然而,我们的研究强调了分析具有纯重复的病例报告在定义表型-基因关系和提高我们对精确染色体区域功能的认识方面的重要性.
We describe a sporadic
case of a pure, tandem, interstitial chromosome 4q duplication, arr[hg19] 4q28.1q32.3 (127,008,069-165,250,477) x3 in a boy born at 36 weeks of gestation. He presented with microcephaly (head circumference <1st percentile), short stature (height <2nd percentile) and poor weight gain (weight <3rd percentile). Hypospadias and horseshoe shaped kidneys were also revealed following a urinary tract ultrasound. Biochemical analysis revealed normal growth hormone and thyroid hormone levels. While gross and fine motor skill development was in line with his age, speech delay was observed. This patient adds to a group of more than 30 cases of pure 4q tandem duplication with common and differing phenotypic presentations. Using a retrospective analysis of previous
case studies alongside the current
case and bioinformatics analysis of the duplicated region, we deduced the most likely dosage sensitive genes for some of the major phenotypes in the patient. The positive predictive value (PPV) was calculated for each gene and phenotype and was derived by comparing the previously reported patients who have gene duplications and an associated phenotype versus those who had the gene duplications but were unaffected. Thus, the growth retardation phenotype may be associated with NAA15 duplication, speech delay with GRIA2 and microcephaly with PLK4 duplication. Functional studies will help in confirming the observations and elucidating the mechanisms. However, our study highlights the importance of analysing
case reports with pure duplications in defining phenotype-gene relationships and in improving our knowledge of the function of precise chromosomal regions.