Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.

Our results show that the molecular basis of microcephaly is heterogeneous; thus, the Iranian population may provide a unique source for the identification of further genes underlying this disorder.

Human cytomegalovirus (hCMV) has been described as an important etiological agent of intrauterine infection in women of childbearing age that causes congenital malformation. In the present study we examined 844 serum samples from women of child-bearing age for the presence of IgM and IgG antibodies against hCMV by Elisa technique. 764 out of 844 (93%) of the cases were seropositive for hCMV-IgG and 45 (5.4%) cases were seropositive for hCMV-IgM. An increase in the rate of IgG seroprevalance was associated with an increase in age and parity. The IgG seroprevalance rate was inversely proportional to increasing abortions. Intrestingly seasonal variation affected IgG seroprevalance. There was an increasing trend in IgM positivity rate with age in women less than 29 years. hCMV seroprevalence rate was higher in women from rural as compared to those of urban areas. Finally hCMV primary infections occured in 2.4 % of all pregnancis and it is estimated that up to 0.3% of all congenital disorders, through out Fars province, were due to hCMV. We suggest a role of child to mother hCMV transmission and sexual maturity as the most probable epidemiological factors of hCMV seroprevalence among women of child bearing age.

PTRH2 deficiency is associated with an extremely rare disease, infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We report the first Iranian patient with IMNEPD. We detected a pathogenic variant in the PTRH2 gene (NM_016077.5: c.68T > C, p.V23A). The proband has myopia, spastic diplegic cerebral palsy, urolithiasis, and a history of seizures.