Goyal Manisha, Faruq Mohammed, Gupta Ashok, Shrivastava Divya, Shamim Uzma
Department of Pediatrics, Centre of Rare Diseases, SMS Medical College, Jaipur, Rajasthan, India.
CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.
Ann Indian Acad Neurol. 2022 Nov-Dec;25(6):1067-1074. doi: 10.4103/aian.aian_202_22. Epub 2022 Nov 17.
A prospective study using array CGH in children with Syndromic microcephaly from a tertiary pediatric healthcare centre in India.
To identify the copy number variations causative of microcephaly detected through chromosomal array CGH.
Of the 60 patients, 33 (55%) males and 27 (45%) females who consulted the Rare Disease Clinic at Department of Pediatrics, SMS Medical College, Jaipur, with developmental delay/facial dysmorphism/congenital anomalies in combination with microcephaly were included.
Children with acquired or non-genetic causes of microcephaly, craniosynostosis, metabolic diseases, known chromosomal aneuploidy such as trisomy 21, 13, and 18 and abnormal karyotype were excluded. The cohort was analyzed by array CGH in order to identify potentially pathogenic copy number variants (CNVs).
Clinically relevant pathogenic or likely pathogenic copy number variations (CNVs) were identified in 20/60 (33.3%) patients, variant of uncertain significance (VOUS) in 4/60 (6.6%) cases and benign CNVs in 3/60 (5%) of total cases. Out of 20 cases with pathogenic CNVs, 12 (60%) patients detected with a deletion, five (25%) patients with duplication and three (15%) patients resulted with a complex chromosomal rearrangement. Twelve cases present CNVs containing genes known to be implicated in microcephaly etiology.
This research highlights the contribution of submicroscopic chromosomal changes in the etiology of microcephaly in combination with developmental delay/facial dysmorphism/congenital anomalies (syndromic microcephaly). Our studies provide more insights into the benefits derived by using array CGH analysis in patients with syndromic microcephaly.
在印度一家三级儿科医疗中心，对患有综合征型小头畸形的儿童进行了一项使用阵列比较基因组杂交技术（array CGH）的前瞻性研究。
通过染色体阵列比较基因组杂交技术（array CGH），确定导致小头畸形的拷贝数变异。
纳入了60例患者，其中33例（55%）为男性，27例（45%）为女性，他们因发育迟缓/面部畸形/先天性异常合并小头畸形而到斋浦尔SMS医学院儿科罕见病诊所就诊。
排除因后天性或非遗传原因导致小头畸形、颅缝早闭、代谢性疾病、已知染色体非整倍体（如21三体、13三体和18三体）以及核型异常的儿童。对该队列进行阵列比较基因组杂交技术（array CGH）分析，以确定潜在的致病拷贝数变异（CNV）。
在60例患者中，20例（33.3%）鉴定出临床相关的致病或可能致病的拷贝数变异（CNV），4例（6.6%）为意义未明的变异（VOUS），3例（5%）为良性CNV。在20例致病CNV的病例中，12例（60%）患者检测到缺失，5例（25%）患者检测到重复，3例（15%）患者出现复杂的染色体重排。12例病例的CNV包含已知与小头畸形病因相关的基因。
本研究突出了亚显微染色体变化在小头畸形病因中与发育迟缓/面部畸形/先天性异常（综合征型小头畸形）的结合中所起的作用。我们的研究为在综合征型小头畸形患者中使用阵列比较基因组杂交技术（array CGH）分析所带来的益处提供了更多见解。
