Supplementary Material for: Gray Matter Heterotopia, Mental Retardation, Developmental Delay, Microcephaly, and Facial Dysmorphisms in a Boy with Ring Chromosome 6: A 10-Year Follow-Up and Literature Review

Ring chromosome 6, r(6), is an extremely rare cytogenetic abnormality with clinical heterogeneity which arises typically de novo. The phenotypes of r(6) can be highly variable, ranging from almost normal to severe malformations and neurological defects. Up to now, only 33 cases have been reported in the literature. In this 10-year follow-up study, we report a case presenting distinctive facial features, severe developmental delay, and gray matter heterotopia with r(6) and terminal deletions of 6p25.3 (115426-384174, 268 kb) and 6q26-27 (168697778-170732033, 2.03 Mb) encompassing 2 and 15 candidate genes, respectively, which were detected using G-banding karyotyping, FISH, and chromosomal microarray analysis. We also analyzed the available information on the clinical features of the reported r(6) cases in order to provide more valuable information on genotype-phenotype correlations. To the best of our knowledge, this is the first report of gray matter heterotopia manifested in a patient with r(6) in China, and the deletions of 6p and 6q in our case are the smallest with the precise size of euchromatic material loss currently known.

6号环状染色体（Ring chromosome 6, r(6)）是一类极为罕见的细胞遗传学异常，具有显著临床异质性，通常为新发产生。r(6)相关表型差异悬殊，可表现为近乎正常，亦可出现严重畸形与神经系统缺陷。截至目前，文献中仅报道过33例此类病例。本项为期10年的随访研究报道了1例携带r(6)及6p25.3（115426-384174，268 kb）、6q26-27（168697778-170732033，2.03 Mb）末端缺失的患者：该患者表现为特征性面容、重度发育迟缓以及灰质异位（gray matter heterotopia），上述染色体异常通过G显带核型分析、荧光原位杂交（Fluorescence in situ hybridization, FISH）与染色体微阵列分析得以检出，其分别携带2个和15个候选基因。本研究同时整理分析了已报道的r(6)病例的临床特征资料，旨在为基因型-表型关联的相关研究提供更具价值的参考依据。据我们所知，本研究是国内首次报道合并灰质异位的r(6)患者，且本病例中6p与6q的缺失是目前已知的、精确明确了常染色质物质缺失范围的最小片段缺失。