In a 10-year-old boy (family 13DG0215), born of consanguineous parents, with infantile-onset multisystem neurologic, endocrine, and pancreatic disease-1 (IMNEPD1; 616263), Alazami et al. (2015) identified a homozygous c.254A-C transversion in the PTRH2 gene, resulting in a gln85-to-pro (Q85P) substitution. A brother was similarly affected. Functional studies of the variant were not performed. The patient had global developmental delay, hypotonia, hearing loss, and ataxia; pancreatic exocrine dysfunction was not reported. The patient was part of a large cohort of 143 multiplex consanguineous families with various neurodevelopmental disorders who underwent whole-exome sequencing.
Picker-Minh et al. (2016) identified homozygosity for the c.254A-C transversion (c.254A-C, NM_016077.4) in exon 2 of the PTRH2 gene, resulting in a Q85P substitution, in 5 patients from 2 unrelated highly consanguineous kindreds of Tunisian and Saudi Arabian descent with IMNEPD1. Fibroblasts derived from 1 of the patients showed normal PTRH2 mRNA levels, but decreased protein levels.
Sharkia et al. (2017) identified homozygosity for the Q85P mutation in the PTRH2 gene in 3 sibs, born of consanguineous Arab parents, with IMNEPD1. The mutation, which was found by a combination of homozygosity mapping and exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Functional studies of the variant and studies of patient cells were not performed. Clinical variability was observed.
