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A novel homozygous splice‐site variant of NCAPD2 gene identified in two siblings with primary microcephaly: The second case report
Author(s) -
Lin Yunting,
Zeng Chunhua,
Lu Zhikun,
Lin Ruizhu,
Liu Li
Publication year - 2019
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13559
Subject(s) - microcephaly , proband , genetics , sanger sequencing , compound heterozygosity , biology , exome sequencing , gene , splice , splice site mutation , allele , mutation , rna splicing , rna
Here we describe the second case of primary microcephaly caused by a novel homozygous splice‐site variant at the NCAPD2 gene. The proband was born with microcephaly, and developed intellectual disability. Whole exome sequencing identified a canonical splice‐site variant, c.3477+2T>C, at the NCAPD2 gene. Sanger sequencing showed that the proband and her sibling, a symptomatic fetus, carried a homozygous c.3477+2T>C variant, while the unaffected parents were heterozygous and her younger brother had wild‐type alleles. To date, only one case of primary microcephaly with a homozygous splice‐site pathogenic variant at the NCAPD2 gene has been reported. Our study of two siblings provides additional evidence that NCAPD2 is a causative gene of primary microcephaly. This finding adds new knowledge in the etiology of microcephaly and contributes to more accurate counseling of affected families.

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