Identification of a novel hemizygous missense RPL10 gene variant in two unrelated patients

Lixia Xu¹Ke Wu¹Cong Yan^2*

• ¹Quzhou Maternity and Child Health Care Hospital, Quzhou, China
• ²Yiwu Maternity and Children Health Care Hospital, Jinhua, Zhejiang Province, China

The X-linked syndromic intellectual developmental disorder-35 (MRXS35; MIM#300998) is caused by variants in the RPL10 gene (312173) on chromosome Xq28. Patients with MRXS35 mainly present with intellectual disability (ID), psychomotor development delay, speech delay, short stature, cranio-facial features, hypotonia, seizures, gastrointestinal problems, genitourinary anomalies, cardiac anomalies, eye defects, hearing loss. Herein, we first reported two unrelated Chinese patients with the same novel hemizygous missense RPL10 gene variant. Two male patients from two different families were admitted to the hospital and sought for genetic counselling. In the first months of life, both newborns presented with congenital laryngeal stridor, feeding difficulties, neonatal pneumonia, neonatal hypoglycemia, dysmorphic features and bilateral cryptorchidism. At the last clinical evaluation at 9 years of age, the male case Ⅱ presented with ID, speech delay, short stature, cranio-facial features. Whole exome sequencing (WES) identified the same hemizygous missense RPL10 gene variant (NM_006013.5:c.347G>A, p.Arg116Gln) inherited from their own mother. Functional analysis of this variant in vitro demonstrated that this missense RPL10 gene variant (c.347G>A) reduced the mRNA expression of RPL10 gene, thereby decreasing the synthesis of the RPL10 protein. Our functional analysis in vitro indicated a loss-of-function effect of RPL10 gene variants.