<scp>p.His165Pro</scp>: A novel <scp>SOX9</scp> missense mutation of campomelic dysplasia

Tonni, Gabriele; Ventura, Alessandro; Pattacini, Pierpaolo; Bonasoni, Maria Paola; Baffico, Ave Maria

doi:10.1111/jog.12032

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Understanding the underlying molecular etiologies was very helpful in classification of specific types of genetic skeletal disorders. The newly discovered mutations in previous literatures and our study have greatly enriched the mutation spectrum of SD, 41–45 which benefit to the genetic diagnosis and consultation of this disease.…”

Section: Discussionmentioning

confidence: 70%

Prenatal ultrasound findings and prenatal diagnosis of fetal skeletal dysplasia

Li,

Jin,

Liu

et al. 2024

J of Clinical Ultrasound

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ObjectiveTo analyze the value of prenatal ultrasound and molecular testing in diagnosing fetal skeletal dysplasia (SD).MethodsClinical data, prenatal ultrasound data, and molecular results of pregnant women with fetal SD were collected in the ultrasound department of our clinic from May 2019 to December 2021.ResultsA total of 40 pregnant women with fetal SD were included, with 82.5% exhibiting short limb deformity, followed by 25.0% with central nervous system malformations, 17.50% with facial malformations, 15% with cardiac malformations, and 12.5% with urinary system malformations. The genetic testing positive rate was 70.0% (28/40), with 92.8% (26/28) being single‐gene disorders due to mutations in FGFR3, COL1A1, COL1A2, EVC2, FLNB, LBR, and TRPV4 genes. The most common SD subtypes were osteogenesis imperfecta (OI), thanatophoric dysplasia (TD), and achondroplasia (ACH). The gestational age (GA) at initial diagnosis for TD, OI, and ACH was 16.6, 20.9, and 28.3 weeks, respectively (p < 0.05), with no significant difference in femoral shortening between the three groups (p > 0.05). Of the OI cases, 5 out of 12 had a family history.ConclusionShort limb deformity is the most prevalent phenotype of SD. When fetal SD is suspected, detailed ultrasound screening should be conducted, combined with GA at initial diagnosis, family history, and molecular evidence, to facilitate more accurate diagnosis and enhance prenatal counseling and perinatal management.

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Section: Discussionmentioning

confidence: 70%

Prenatal ultrasound findings and prenatal diagnosis of fetal skeletal dysplasia

Li,

Jin,

Liu

et al. 2024

J of Clinical Ultrasound

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“…Since changes in SOX9 associated with CD are mainly private mutations, the alterations identified here expand the spectrum of SOX9 pathogenic variations to about seventy ( Table S3 ) ( Thong et al , 2000 ; Giordano et al , 2001 ; Preiss et al , 2001 ; Sock et al , 2003 ; Michel-Calemard et al , 2004 ; Hsiao et al , 2006 ; Shotelersuk et al , 2006 ; Beaulieu et al , 2009 ; Gentilin et al , 2010 ; Okamoto et al , 2010 ; Staffler et al , 2010 ; Kim et al , 2011 ; Stoeva et al , 2011 ; Chen et al , 2012 ; Gopakumar et al , 2013 ; Matsushita et al , 2013 ; Tonni et al , 2013 ). Premature termination codons (PTCs) are the most prevalent mutational class in CD, accounting for approximately 45% of all the alterations identified.…”

Section: Discussionmentioning

confidence: 84%

Clinical and molecular characterization of a Brazilian cohort of campomelic dysplasia patients, and identification of seven new SOX9 mutations

et al. 2015

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Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46, XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.

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“…Commonly, prenatal diagnosis of CD is made in the second trimester of pregnancy: Promsonthi and Wattanasirichaigoon (2006) reported a 3D ultrasound diagnosis made at 26 weeks' gestation and emphasized the advantages of the surface-rendering mode of 3D ultrasound in evaluating fetal skeletal dysplasia; Gentilin et al (2010) described five cases prenatally detected between 12 and 32 weeks in which the diagnosis was confirmed by molecular analysis of SOX9 gene; Tonni et al (2013) reported a previously unreported de novo missense mutation in p.His165Pro in a fetus with severe bowing of the long bones, cystic hygroma, Pierre Robin sequence, bilateral hydronephrosis and ascites. Massardier et al (2008) reported two cases suspected at the 13 th week and presented with hygroma colli along with anomalies in the lower but not the upper limbs: when first trimester hygroma colli is accompanied by specific findings of the lower limbs, the diagnosis of CD can be investigated through SOX9 mutation analysis.…”

mentioning

confidence: 99%