A novel SMOC1 pathogenic homozygous variant in a fetus with mesomelia of the lower limbs, micrognathia and hypertelorism and an incidental finding of CYP21A2-related congenital adrenal hyperplasia.

Autor: Willison C; North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Ramachandran V; North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Chandler NJ; North Thames Genomic Laboratory Hub, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Hillman S; Institute for Women's Health, University College London, London, UK.; University College London Hospitals, London, UK., Ashraf T; Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Jazyk: angličtina
Zdroj: Prenatal diagnosis [Prenat Diagn] 2023 Dec; Vol. 43 (13), pp. 1674-1677. Date of Electronic Publication: 2023 Dec 07.
DOI: 10.1002/pd.6485
Abstrakt: Trio exome sequencing was performed on a fetus with bilateral mesomelia of the lower limbs with significant angulation of the tibial bones, micrognathia and hypertelorism detected on ultrasound scan at 19 + 0 weeks gestation. The couple is consanguineous. A homozygous pathogenic frameshift variant in the SMOC1 gene (c.339_340del p.(Phe114Cysfs*40)) was detected and both parents were shown to be heterozygous. Pathogenic variants in the SMOC1 gene are associated with microphthalmia with limb anomalies which multidisciplinary team discussion determined to be causal of the scan anomalies detected. The fetus was also a compound heterozygote for CYP21A2 pathogenic variants, confirming a second diagnosis of non-classical congenital adrenal hyperplasia, which was felt incidental to the scan findings. The risk that this couple's next pregnancy would be affected by either of these disorders is 1 in 4 (25%) and demonstrates the importance of genetic diagnoses for the family and implications for future pregnancies.
(© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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