Hussen Dalia F, Kamel Alaa K, Mekkawy Mona K, Ashaat Engy A, El Ruby Mona O
Human Cytogenetics Department, National Research Centre, Cairo, Egypt.
Clinical Genetics Department, National Research Centre, Cairo, Egypt.
Mol Syndromol. 2020 Dec;11(5-6):284-295. doi: 10.1159/000510428. Epub 2020 Sep 23.
Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.
1p36单体综合征是最常见的亚微观缺失综合征之一，其特征为发育里程碑延迟、智力障碍以及临床上可识别的颅面部畸形特征。该综合征包括4种细胞遗传学类型，即单纯末端缺失、中间缺失、复杂重排以及因不平衡易位产生的衍生1号染色体，其中不平衡易位在所有1p36单体病例中所占比例最小（7%）。大多数因不平衡易位导致1p36单体的患者可通过传统技术进行细胞遗传学诊断。然而，在这些病例中必须进行染色体微阵列分析，以检测缺失的拷贝数变异和大小，并有助于建立表型-基因型相关性。在此，我们研究了一名1.5岁的女性患者，她表现出智力障碍、发育里程碑延迟、肌张力减退、癫痫发作以及特征性的畸形特征，包括短头畸形、眉毛平直、眼窝深陷、睑裂下斜、面中部发育不全、鼻梁凹陷、人中长和下巴尖。进行了传统细胞遗传学分析（CCA）、微阵列研究和荧光原位杂交（FISH）分析。CCA显示1号和21号染色体发生易位，核型为45,XX,der(1)t(1;21)(p36.32;q21.1)dn。微阵列分析显示1p36和21q近端均存在拷贝数缺失。FISH证实了1p36缺失的存在，但未对21q进行检测。我们得出结论，1p36单体综合征的表型-基因型相关性可针对基本临床表现进行；然而，该综合征的最终表现取决于综合因素。因不平衡易位导致的1p36单体可能表现为典型症状，也可能根据涉及不同染色体的拷贝数变异而出现各种严重程度的其他改变特征。
