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Hydrocephaly associated with compound heterozygous alterations in TRAPPC12
Author(s) -
Gass Jennifer M.,
Head Barbara B.,
Shields Sally M.,
Stevenson Roger E.,
Louie Raymond J.
Publication year - 2020
Publication title -
birth defects research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.845
H-Index - 17
ISSN - 2472-1727
DOI - 10.1002/bdr2.1699
Subject(s) - fetus , hydrocephalus , exome sequencing , biology , compound heterozygosity , holoprosencephaly , gene , cerebrospinal fluid , genetics , pregnancy , andrology , allele , medicine , mutation , neuroscience , radiology
Background Hydrocephalus is characterized by increased cerebrospinal fluid within the brain, a causally heterogeneous disorder estimated to affect 1 per 1,000 live births, with the most severe cases often leading to fetal demise. The large number of known genetic and environmental factors that contribute to hydrocephalus makes the differential diagnosis challenging. Cases Three consecutive pregnancies of an unrelated couple were found by ultrasound to carry fetuses with hydrocephaly. DNA from two affected fetuses and the parents were subjected to whole exome sequencing. Heterozygous alterations in the TRAPPC12 gene were identified in the parents and compound heterozygous alterations were present in the two affected fetuses. The variant from the father (c.954del) leads to a premature termination of the transcript; the variant from the mother (c.1677+5G>A) affects a splice site which leads to aberrant splicing of the TRAPPC12 transcript. Conclusion Compound heterozygous variants in TRAPPC12 , which encodes a protein involved in Golgi trafficking and mitosis, may disrupt normal brain embryogenesis leading to hydrocephalus and recurrent pregnancy loss.