Kahrizi Syndrome

A number sign (#) is used with this entry because Kahrizi syndrome (KHRZ) can be caused by homozygous mutation in the SRD5A3 gene (611715) on chromosome 4q12.

Description

Kahrizi syndrome is an autosomal recessive neurodevelopmental disorder characterized by mental retardation, cataracts, coloboma, kyphosis, and coarse facial features (summary by Kahrizi et al., 2009).

See also congenital disorder of glycosylation type Iq (CDG1Q; 612379), an allelic disorder with overlapping features.

Clinical Features

Kahrizi et al. (2009) reported 3 Iranian sibs with a syndrome characterized by severe mental retardation, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. One sib had left iris coloboma, and another sib had bilateral iris coloboma. At the time of the report, the patients were 45, 42, and 40 years old. None of the patients had learned to speak, and their motor development was delayed. All 3 sibs developed severe thoracic kyphosis at about 8 years of age, but skeletal X-rays revealed no vertebral abnormalities. They also developed contractures of the knee and elbow joints. The oldest brother had a large capillary hemangioma on the left cheek. Seizures and other neurologic problems were not reported. Both parents came from the same village in central Iran and were presumably related, although the precise relationship could not be determined. Kahrizi et al. (2009) assumed a third-cousin relationship for linkage analysis.

Mapping

By linkage analysis, followed by haplotype analysis, of an Iranian family with syndromic mental retardation, Kahrizi et al. (2009) identified a 10.4-Mb region of homozygosity on chromosome 4p12-q12 between SNPs rs728293 and rs1105434 (parametric lod score of 3.38; nonparametric lod score of 4.53).

Molecular Genetics

In 3 sibs, born of consanguineous Iranian parents, with Kahrizi syndrome (Kahrizi et al., 2009), Kahrizi et al. (2011}) identified a homozygous truncating mutation in the SRD5A3 gene (611715.0006). RT-PCR analysis showed missing or reduced expression of the SRD5A3 gene in patient lymphoblastoid cells. However, biochemical studies showed no clear abnormal transferrin mobility in routine testing for congenital defects of glycosylation. The mutation was identified by array-based exon enrichment and next-generation sequencing.