Year: 2014
Type: article
Abstract: Novel c.358C>T mutation of SOX9 gene in prenatal diagnosis of campomelic dysplasiaDear Editor, We report a case of a 30-year-old primigravida, with unremarkable family history, who had an ultrasound examination at 19 weeks, revealing a fetus with bowed long bones of the lower limbs (Fig. 1a), angulated tibiae, clubfeet, micrognathia, unilateral choroid plexus cyst (8 mm) and bilateral renal pyelectasis (8 mm).Fetal karyotype was 46,XX.Growth parameters were: biparietal diameter 45 mm (50 th ), head circumference (HC) 150 mm (50 th ), abdominal circumference 160 mm (50 th ), femur 23 mm (10 th ), tibia 13 mm (<5 th ), fibula 10 mm (<5 th ), humerus 17 mm (10 th ).No other thoracic, abdominal and/or extraskeletal congenital malformations were detected.The pregnancy was terminated at the 21 st week.Fetal examination revealed: total length 21 cm (<5 th ), foot length 2.8 cm (<5 th ), HC 17 cm (10 th ), weight 250 g (10 th ), thigh length 5 cm, leg length 3.5 cm, low-set ears, flat face, short nose and anteverted nostrils, microretrognathia, bowed femora, osseous spikes at the middle of both tibia, clubfeet and 11 pairs of short ribs (Fig. 1b).Molecular analysis identified a de novo heterozygous c.358C>T transition in exon 1 of SRY-box 9 (SOX9) gene that lead to campomelic dysplasia (CD) by substitution of arginine at position 120 to the polar neutral cysteine (Fig. 2a).This missense mutation of High Mobility Group DNA-binding domain of the protein could cause CD by haploinsufficiency or either reduce or abolish the DNA-binding ability of the mutant SOX9 protein (Fig. 2b).Replacement of the previous aminoacid, Ala119Val, has been described to cause CD (Jakubiczka et al. 2001).Campomelic dysplasia is generally characterized by bowing of femora and tibiae, hypoplastic scapulae, small thorax with 11 pairs of slender ribs, pelvic malformations and club feet.Radiological features include hypoplastic vertebral bodies, abnormal cervical vertebrae, kyphoscoliosis, absence of mineralization of the thoracic pedicles and vertical narrow iliac wings.Other characteristics are macrocephaly, hypertelorism, depressed nasal bridge, low-set ears, Robin sequence, cleft palate and flat face (Mansour et al. 2002).Two-thirds of XY individuals with CD have either sex reversal or genital defects (Wagner et al. 1994).In prenatal period, CD is characterized by the shortening and marked anterior bowing of femur and tibia.Increased nuchal translucency, ventriculomegaly, cardiac and renal anomalies and late polyhydramnios have also been described (Massardier et al. 2008).Families with recurrence have been described and somatic and germline mutations have been confirmed in a few families (Wagner et al. 1994;Gentilin et al. 2010).SOX9 mutations were scattered throughout the three exons with missense, nonsense, frameshift and splice-site mutations, but there did not appear to be any obvious correlation between the mutation's features and the condition's severity.Frameshift and many nonsense SOX9 mutations predict a prematurely truncated protein that misses TA domain and all, or part, of the HMG domain.Missense mutations are exclusively located in the HMG domain, affecting the
Source: Congenital Anomalies
DOI: 10.1111/cga.12054
Institutions: Ospedale Garibaldi, Ente Ospedaliero Ospedali Galliera
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2123220022