Case Report: Identification of a novel hemizygous missense gene variant in two unrelated patients.

The X-linked syndromic intellectual developmental disorder-35 (MRXS35; OMIM#300998) is caused by variants in the gene (OMIM*312173) on chromosome Xq28. Patients with MRXS35 mainly present with intellectual disability (ID), psychomotor development delay, speech delay, short stature, craniofacial anomalies, hypotonia, seizures, gastrointestinal problems, genitourinary anomalies, cardiac anomalies, eye defects, and hearing loss. Herein, we are the first to report two unrelated Chinese patients with the same novel hemizygous missense gene variant. Two male patients from two different families were admitted to the hospital for genetic counseling. 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 his last clinical evaluation at 9 years of age, case II presented with ID, speech delay, short stature, and craniofacial anomalies. Whole-exome sequencing identified the same hemizygous missense gene variant (NM_006013.5:c.347G>A, p.Arg116Gln) in each patient, inherited from their respective mothers. The functional analysis of this variant demonstrated that this missense gene variant (c.347G>A) reduced the mRNA expression of the gene, thereby decreasing synthesis of the RPL10 protein. Our functional analysis indicated a loss-of-function effect of gene variants.