Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant.

Autor: El-Dessouky SH; Prenatal Diagnosis and Fetal Medicine Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt., Issa MY; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt., Aboulghar MM; Department of Obstetrics and Gynecology, Fetal Medicine Unit, Cairo University, Cairo, Egypt., Gaafar HM; Department of Obstetrics and Gynecology, Fetal Medicine Unit, Cairo University, Cairo, Egypt., Elarab AE; Department of Obstetrics and Gynecology, Fetal Medicine Unit, Cairo University, Cairo, Egypt., Ateya MI; Department of Obstetrics and Gynecology, Fetal Medicine Unit, Cairo University, Cairo, Egypt., Omar HH; Diagnostic and Research Department, Centogene AG, Rostock, Germany., Beetz C; Diagnostic and Research Department, Centogene AG, Rostock, Germany., Zaki MS; Clinical Genetics Department, Human Genetics and Genome Research Division, National Research Centre, Cairo, Egypt.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2020 Dec; Vol. 182 (12), pp. 2867-2876. Date of Electronic Publication: 2020 Sep 10.
DOI: 10.1002/ajmg.a.61858
Abstrakt: Kinase D-interacting substrate of 220 kDa (KIDINS220) is a transmembrane protein playing integral role in growth mediating pathways in the nervous and cardiovascular systems. KIDINS220 heterozygous truncating variants that affect the protein's C-terminus have been associated with a phenotype, so far described only in few unrelated children, including spastic paraplegia, intellectual disability, nystagmus, and obesity. More recently, a homozygous, more N-terminal truncating variant in KIDINS220 gene was suggested to be associated with enlarged cerebral ventricles and limb contractures in three fetuses from a consanguineous family. We confirm the latter finding by presenting the first detailed prenatal identification of a fetal phenotype associated with novel homozygous deleterious frameshift variant in KIDINS220 gene in a consanguineous healthy Egyptian couple. History of unexplained seven miscarriages and a similar stillbirth were recorded. Prenatal ultrasonography revealed limb contractions and ventriculomegaly; in addition to previously unreported cerebellar anomalies, cardiac anomalies and hydrops fetalis. These findings represent an expansion of clinical and molecular spectrum associated with KIDINS220 variants and broaden our understanding of genotype-phenotype relationships in lethal congenital contractures syndromes and associated severe abnormal embryological development. More generally, our study adds KIDINS220 to the rare group of genes which may cause disease by either of two distinct mutational mechanisms.
(© 2020 Wiley Periodicals LLC.)
Databáze: MEDLINE
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