A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies.
Bottom Line: Combining the four families in linkage analysis confirmed a significant genome-wide linkage signal at the CEP120 locus.In addition, we show marked reduction of cilia and abnormal number of centrioles in fibroblasts from one affected individual.We also demonstrate that in CEP120 morphants, cilia are shortened in the neural tube and disorganized in the pronephros.
Affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.Show MeSH
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Mentions: The first individual (Family 1_II:2) is a female stillbirth who was born vaginally at 35 weeks of gestation to healthy first-cousin Saudi parents. In addition to a severely narrow chest, apparent physical anomalies included relative macrocephaly, hypertelorism, scant eyebrows, a mild cleft lip (notch), short limbs and synpolydactyly (Figs 1A–D and 2A). Radiological examination revealed a narrow thorax with very short and horizontal ribs, a relatively normal spine, dysplastic and small pelvic bones with a narrow sciatic notch bilaterally, round ended femur bones, small tibia and fibula, pre-axial polydactyly and extremely hypoplastic middle and distal phalanges. She died at 5 h of age due to severe cardiopulmonary insufficiency and autopsy was declined. The second individual (Family 2_II:4) is a male baby born to healthy first-cousin Saudi parents who have a healthy child but had an intrauterine fetal death with skeletal dysplasia and pre-axial polydactyly. The similarity with the index case in Family 1 was striking in that there was a very narrow chest, short extremities and synpolydactyly. However, he lacked cleft lip but instead had tongue hamartoma (lobulated tongue) and omphalocele. His skeletal radiological findings included small facial bones, narrow thorax with small and horizontal ribs, flaring of the iliac bones with trident sciatic notch, short long bones of the upper and lower limbs and pre-axial polydactyly. Brain magnetic resonance imaging (MRI) showed cerebellar hypoplasia with Dandy-Walker malformation and extra-axial fluid collection. Abdominal ultrasound was normal as was electroretinography (ERG; Figs 1E–H and 2A). He later succumbed to cardiopulmonary insufficiency. Again, the family declined autopsy.Figure 1.
Affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.