The role of autosomal recessive (AR) variants in clinically heterogeneous conditions such as intellectual disability and developmental delay (ID/DD) has been difficult to uncover. Implication of causative pathogenic AR variants often requires investigation within large and consanguineous families, and/or identifying rare biallelic variants in affected individuals. Furthermore, detection of homozygous gene-level copy number variants during first-line genomic microarray testing in the pediatric population is a rare finding. We describe a 6.7-year-old male patient with ID/DD and a novel homozygous deletion involving the FRY gene identified by genomic SNP microarray. This deletion was observed within a large region of homozygosity on the long arm of chromosome 13 and in a background of increased low-level (2.6%) autosomal homozygosity, consistent with a reported common ancestry in the family. FRY encodes a protein that regulates cell cytoskeletal dynamics, functions in chromosomal alignment in mitosis in vitro, and has been shown to function in the nervous system in vivo. Homozygous mutation of FRY has been previously reported in 2 consanguineous families from studies of autosomal recessive ID in Middle Eastern and Northern African populations. This report provides additional supportive evidence that deleterious biallelic mutation of FRY is associated with ID/DD and illustrates the utility of genomic SNP microarray detection of low-level homozygosity.

中文翻译：

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与非综合征性发育迟缓相关的 FRY 基因内新的纯合缺失

常染色体隐性 (AR) 变异在智力障碍和发育迟缓 (ID/DD) 等临床异质性疾病中的作用一直难以揭示。致病性 AR 变异的含义通常需要在大家族和近亲家族中进行调查，和/或在受影响的个体中鉴定罕见的双等位基因变异。此外，在儿科人群的一线基因组微阵列测试期间检测纯合基因水平拷贝数变异是一个罕见的发现。我们描述了一名 6.7 岁男性患者，患有 ID/DD 和一种新型纯合缺失，涉及基因组 SNP 微阵列确定的 FRY 基因。这种缺失是在 13 号染色体长臂的大范围纯合子区域内观察到的，并且在低水平 (2.6%) 常染色体纯合子增加的背景下，与所报道的家族共同血统一致。FRY 编码一种调节细胞骨架动力学的蛋白质，在体外有丝分裂的染色体排列中起作用，并且已被证明在体内神经系统中起作用。FRY 的纯合突变先前已在中东和北非人群常染色体隐性 ID 的研究中在 2 个近亲家族中报告。该报告提供了额外的支持性证据，表明 FRY 的有害双等位基因突变与 ID/DD 相关，并说明了基因组 SNP 微阵列检测低水平纯合性的效用。FRY 的纯合突变先前已在中东和北非人群常染色体隐性 ID 的研究中在 2 个近亲家族中报告。该报告提供了额外的支持性证据，表明 FRY 的有害双等位基因突变与 ID/DD 相关，并说明了基因组 SNP 微阵列检测低水平纯合性的效用。FRY 的纯合突变先前已在中东和北非人群常染色体隐性 ID 的研究中在 2 个近亲家族中报告。该报告提供了额外的支持性证据，表明 FRY 的有害双等位基因突变与 ID/DD 相关，并说明了基因组 SNP 微阵列检测低水平纯合性的效用。