Introduction: Autosomal recessive primary microcephaly is a condition in which infants are born with a very small head and a small brain. Autosomal recessive primary microcephaly causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. As the advanced genetic technologies, the underlying molecular causes of autosomal recessive primary microcephaly have been recently elucidated. We here report a case of primary microcephaly with two novel mutations in WDR62 gene
Case: A 6-year-old girl was referred in the outpatient rehabilitation clinic because of microcephaly and delayed development. The patient had been born at 36+4 weeks of gestation by caesarean section. The birth weight was 1800g (<1st percentile). On the prenatal course, intrauterine growth restriction was detected on ultrasonography test. The patient had one older sibling, who has no microcephaly and developmental abnormality. On the examination, delayed speech development and microcephaly with occipitofrontal head circumference of 43.5cm (< -3SD, Fig 1) was noted. Her gross and fine motor development was normal. On Preschool Receptive-Expressive Language Scale (PRES), expressive and receptive language of 41 months was revealed. Korean-Leiter International performance Scale - Revised (K-LIP-R) examination, IQ was 43 (<0.1 percentile), which indicate the level of 27-month-old. Social maturity scale was 35.5 (SQ=76.92).
Brain CT and MRI was unremarkable. The laboratory findings including organic acids were normal. In chromosomal study, karyotype of 46,XX, inv(9) (p12q13) was revealed, which was benign. Microdeletion syndrome study (Multiplex ligation-dependent probe amplification technique) showed no abnormality. Chromosomal microarray (Affymetrix Cytoscan 750K array, genome build: Hg19 method) was normal. In clinical exome sequencing test, heterozygous two novel variants were found in the WDR62 gene at 2 different sites: in exon 8 (NM_001083961.1: c.883-4_890del) from mother and in exon 13 (NM_001083961.1: c.1684C>G) from father. In addition, patient’s parents were identified as heterozygous carriers for each variation which occurs in trans. Each variation was confirmed by conventional Sanger sequencing. These two novel variations have not been reported in control databases such as the 1,000 Genomes Project, Exome Aggregation Consortium, gnomAD and the dbSNP Database. The proband was diagnosed as autosomal recessive primary microcephaly type 2 based on clinical and molecular findings.
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