Prepair 1000+

Gene: MESP2

Green List (high evidence)

Spondylocostal dysostosis 2 (SCDO) is a condition caused by abnormal development of bones in the spine and ribs, the vertebrae are misshapen and fused, and some rib bones can also be fused. Many people with this condition have scoliosis. Affected individuals have short, rigid necks and short torsos. Infants with this condition have small chests that cannot expand adequately, often leading to life-threatening breathing problems. Affected individuals can also develop inguinal hernia and neural tube defects (spina bifida). Although breathing problems can be fatal early in life, many affected individuals have normal intelligence and a good independent quality of life.
E103X mutation is a founder mutation in Puerto Rican families.

Unsure if MESP2-related spondylothoracic dysostosis (MESP2-STD) should be added as a separate phenotype?
From GeneReviews PMID: 20301771
SCDO: The 4-bp duplication c.500_503dup occurs after the basic helix-loop-helix (bHLH) domain and causes a frameshift resulting in a premature stop codon within the second (and final) MESP2 exon [Whittock et al 2004b]. Transcripts with this pathogenic variant would not be subject to nonsense-mediated decay. Individuals with this pathogenic variant are predicted to have a truncated protein containing an intact bHLH domain, which may retain some function. In contrast, the pathogenic nonsense variants identified in spondylothoracic dysostosis (STD) (see Genetically Related Disorders) are located within the first exon, and the resulting mutated mRNA transcripts are predicted to be susceptible to nonsense-mediated decay. Therefore, persons homozygous or compound heterozygous for these pathogenic nonsense variants are likely to have reduced or absent levels of MESP2 protein, which may account for the difference in severity between the MESP2-related SCDO and STD phenotypes.
Genetically Related (Allelic) Disorder - MESP2-related spondylothoracic dysostosis (MESP2-STD). To date, most individuals reported with MESP2-related STD have had pathogenic nonsense variants in exon 1 of MESP2, which are predicted to result in nonsense-mediated decay; however, several affected individuals have been reported who are heterozygous for a pathogenic nonsense variant and a pathogenic missense variant most individuals reported with MESP2-related STD have had pathogenic nonsense variants in exon 1 of MESP2, which are predicted to result in nonsense-mediated decay; however, several affected individuals have been reported who are heterozygous for a pathogenic nonsense variant and a pathogenic missense variant.

Created: 27 Dec 2024, 4:18 a.m. | Last Modified: 27 Dec 2024, 4:18 a.m.

Panel Version: 1.892

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spondylocostal dysostosis 2, MIM #608681

Publications

• PMID: 18485326
• 15122512
• 20301771