Infantile hypercalcemia is an autosomal recessive disorder caused either by mutations in the CYP24A1 gene (20q13.2) or in the SLC34A1 gene (5q35.3). This disease is characterized by hypercalcemia, hypercalciuria and nephrocalcinosis in paediatric patients. Maternal uniparental disomy of chromosome 20 [UPD(20)mat], resulting in aberrant expression of imprinted transcripts at the GNAS locus, is a poorly characterized condition. UPD(20)mat patients manifest a phenotype similar to that of Silver-Russell syndrome and small for gestational age-short stature. We report here the genetic and clinical characterization of a male child with a phenotype of infantile hypercalcemia, postnatal growth retardation, and minor dysmorphic features. Genetic analysis using a next generation sequencing panel revealed a homozygous pathogenic variant of CYP24A1. The absence of the variant in the father led to microsatellite segregation analysis, suggestive of UPD. SNP-array revealed a large terminal copy neutral loss of heterozygosity leading to CYP24A1 homozygosity. SNP-array data of parent–child trio confirmed a UPD(20)mat responsible for both infantile hypercalcemia and Silver-Russell syndrome-like traits. This is the first report of uniparental disomy of chromosome 20 revealed by infantile hypercalcemia related to CYP24A1 biallelic homozygous variants, underlying the importance of controlling allelic segregation in cases of homozygosity.

中文翻译：

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当CYP24A1基因的母亲杂合突变通过20号染色体的母亲单亲二体性导致婴儿高钙血症时

婴儿高钙血症是由CYP24A1基因（20q13.2）或SLC34A1基因（5q35.3）突变引起的常染色体隐性遗传疾病。该疾病的特征是小儿患者的高钙血症，高钙尿症和肾钙化病。母体单亲二体染色体20 [UPD（20）mat]，导致在GNAS位点的转录物异常表达，是一种特征不明确的疾病。UPD（20）mat患者表现出与Silver-Russell综合征相似的表型，并且对于胎龄短的身材较小。我们在这里报告了一名男婴的遗传和临床特征，该表型为婴儿高钙血症，出生后发育迟缓和轻微畸形。使用下一代测序小组的遗传分析显示CYP24A1的纯合致病性变异。父亲中没有这种变体，导致进行了微卫星偏析，暗示了UPD。SNP数组显示一个大型终端副本中性杂合性丧失导致CYP24A1纯合。亲子三重奏的SNP阵列数据证实，UPD（20）垫可导致婴儿高钙血症和Silver-Russell综合征样特征。这是关于与CYP24A1双等位基因纯合子变异有关的婴儿高钙血症揭示的20号染色体单亲二体性的首次报道，这在控制纯合子情况下具有潜在的控制等位基因分离的重要性。亲子三重奏的SNP阵列数据证实，UPD（20）垫可导致婴儿高钙血症和Silver-Russell综合征样特征。这是关于与CYP24A1双等位基因纯合子变异有关的婴儿高钙血症揭示的20号染色体单亲二体性的首次报道，这在控制纯合子情况下具有潜在的控制等位基因分离的重要性。亲子三重奏的SNP阵列数据证实，UPD（20）垫可导致婴儿高钙血症和Silver-Russell综合征样特征。这是关于与CYP24A1双等位基因纯合子变异有关的婴儿高钙血症揭示的20号染色体单亲二体性的首次报道，这在控制纯合子情况下具有潜在的控制等位基因分离的重要性。