Novel compound heterozygous variants in the LARP7 gene in a patient with Alazami syndrome

Abstract

The LARP7 gene encodes a chaperone protein of the noncoding RNA 75 K, and mutations in this gene have been identified in patients with Alazami syndrome. Herein, we report another Japanese patient with Alazami syndrome and novel compound heterozygous variants in LARP7 (i.e., c.370delG, p.Glu124fs*38 and c.641_667+25del involving the splice donor site of intron 8). These findings provide further evidence that biallelic LARP7 defects cause the phenotype of Alazami syndrome.

Figure 1

Clinical and genetic findings in the patient. (a) A front view of the patient at 2 years of age showing the distinct facial features of a prominent forehead, narrow palpebral fissures, deep-set eyes, hypertelorism, a broad nose and malar hypoplasia. (b) Electropherograms displaying the two LARP7 mutations in the patient. The upper (c.370delG) and lower (c.641_667+25del) sequences are the sense and antisense sequences, respectively. WT, wild-type allele; MT, mutant allele. (c) A schematic representation of the 52-bp deletion (c.641_667+25del) in LARP7. The exonic and intronic sequences are indicated by capital and lower-case letters, respectively. The deleted sequences are shaded in gray. The deletion involved the splice donor site of intron 8 and was predicted to cause an exon skipping of exon 8.