Academic journal article Iranian Journal of Public Health

A Novel Mutation in the OFD1 Gene in a Family with Oral-Facial-Digital Syndrome Type 1: A Case Report

Academic journal article Iranian Journal of Public Health

A Novel Mutation in the OFD1 Gene in a Family with Oral-Facial-Digital Syndrome Type 1: A Case Report

Article excerpt


Orofaciodigital syndrome (OFDS) (OMIM 311200) is a general term for describing several distinctive developmental genetic diseases that are characterized by malformation of the mouth, face and digits. At least 13 different types of the syndrome have been recognized among which type 1 (OFD1) is the most common form with an incidence of 1:50000 to 1:250000 live births (1, 2). The cardinal clinical features include craniofacial abnormalities (facial asymmetry, hypertelorism, frontal bossing, microretrognathia, broadened nasal bridge, cleft palate, multilobulated tongue with nodules, and abnormal dentition), and digital abnormalities including brachydactyly, syndactyly, clinodactyly and preor post-axial polydactyly. In 60% of cases with OFD1, brain structural abnormalities, developmental delay and intellectual disabilities have been identified (3). Majority of cases with onset older than 18 years, suffer from renal cystic disease (4-6). The observation of multiple milia and hypotrichosis is remarkable skin abnormality for OFD1 which are not observed in other types of OFDS (7). Alopecia, deafness and trembling are expressed less frequently in OFD1.

Mutations in the OFD1 gene, which is mapped on chromosome Xp22, are responsible for OFD syndrome type 1. Therefore, OFD syndrome type 1 is inherited in X-linked dominant pattern and has prenatal lethality in the male fetus (5, 8, 9). A protein with 1011 amino acid expressed on the basal body of primary cilia and the centrosome is encoded by OFD1 gene. The protein also has a key role in the biogenesis of cilium and development by modulating Wnt signaling pathways (10-13). To date, over 130 different mutations have been identified in OFD1 with many truncating mutations. The location of mutations causing OFD1 extends to 17 exons of 23 coding exons. About 75% of cases with OFD1 are sporadic, and there are some reports about correlation of genotype with phenotype (12, 14). Mutations in OFD1 gene have also been identified in association with four recessive X-linked phenotypes: Joubert syndrome, intellectual disability, type 2 Simpson-Golabi-Behmel syndrome and retinitis pigmentosa (15-19).

In this case study, we analyzed the sequences of the eight exons of the OFD1 gene in eight individuals from an Iranian family with X-linked dominant OFD1, and we identified a novel mutation. This family had a heterogeneous phenotypic findings ranging from being so mild in the mother that she was undiagnosed to severe neurodevelopmental delay, distinctive dysmorphic facial features, and multiple oral anomalies in her daughters.


The study was approved by Ethics Committee of Yazd University of Medical Sciences and informed written consent was obtained from the all subjects participating in the study.

A female sibship was referred to the Medical Genetics Department of Yazd University of Medical Sciences due to craniofacial and oral dysmorphism in addition to neurodevelopmental delay. The patients were thoroughly examined and all their clinical records were reviewed by a physician. A three-generational pedigree for the family was constructed based on their family history obtained by a genetic counselor (Fig. 1).

Patient 1 (III-VII)

The first patient was a 9-year-old girl with a birth weight of 3200 g who was born to a family with non-consanguineous parents at 37 wk gestation, because of the fourth pregnancy. At birth, she had ventricular septal defect (VSD) diagnosed with fetal ultrasonography, and deformities of the mouth, jaw, and palate were remarkable. The child could stand and walk without assistance at 29 month. She also started to speak her first words at the age of two. At the time of the study, oral abnormalities included cleft palate, malaligned, abnormal dentition, macroglossia, ankyloglossia, multiple hyperplastic frenulums, and a bifid, lobulated tongue. Facial abnormalities that could be seen in the patient were dolichocephaly, macrocephaly (54. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed


An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.