A novel FAM20C mutation causes a rare form of neonatal lethal Raine syndrome

被引:17
作者
Hung, Christina Y. [1 ]
Rodriguez, Mario [2 ]
Roberts, Abra [1 ]
Bauer, Mislen [3 ]
Mihalek, Ivana [4 ]
Bodanner, Olaf [1 ]
机构
[1] Boston Childrens Hosp, Div Genet & Genom, 300 Longwood Ave, Boston, MA 02115 USA
[2] Univ Miami, Hussmann Inst Genom, Miami, FL USA
[3] Nicklas Childrens Hosp, Div Clin Genet & Metab, Miami, FL USA
[4] Univ Rijeka, Dept Mol Med & Biotechnol, Rijeka, Croatia
关键词
FAM20C; osteosclerosis; Raine syndrome; OSTEOSCLEROTIC BONE DYSPLASIA; GENE; OSTEOMALACIA; ANOMALIES; DATABASE; PATIENT;
D O I
10.1002/ajmg.a.61291
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Raine syndrome is a rare, autosomal recessive, osteosclerotic bone dysplasia due to pathogenic variants in FAM20C. The clinical phenotype is characterized by generalized osteosclerosis affecting all bones, cerebral calcifications, and craniofacial dysmorphism. Most cases present during the neonatal period with early lethality due to pulmonary hypoplasia and respiratory compromise while only few affected individuals have been reported to survive into adulthood. FAM20C is a ubiquitously expressed protein kinase that contains five functional domains including a catalytic domain, a binding pocket for FAM20A and three distinct N-glycosylation sites. We report a newborn infant with a history of prenatal onset fractures, generalized osteosclerosis, and craniofacial dysmorphism and early lethality. The clinical presentation was highly suggestive of Raine syndrome. A homozygous, novel missense variant in exon 5 of FAM20C (c.1007T>G; p.Met336Arg) was identified by targeted Sanger sequencing. Following in silico analysis and mapping of the variant on a three-dimensional (3D) model of FAM20C it is predicted to be deleterious and to affect N-glycosylation, protein folding, and subsequent secretion of FAM20C. In addition, we reviewed all published FAM20C mutations and observed that most pathogenic variants affect functional regions within the protein establishing evidence for an emerging genotype-phenotype correlation.
引用
收藏
页码:1866 / 1871
页数:6
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