关键词: 小头畸形-癫痫-发育迟缓症, PNKP基因, 全外显子组基因测序, 遗传家系图谱

Abstract: Objective: To investigate the clinical characteristics of microcephaly, seizures and developmental delay (MCSZ), to analyze the genetic pedigree, to summarize its diagnosis and treatment, and to improve the understanding of the clinicians for MCSZ.Methods: The clinical data of a child with MCSZ were collected and brain MRI plain scan was performed. The blood samples of the patient and his parents were collected for whole exome gene sequencing.Results: The clinical manifestations of the patient were small anterior fontanel and head circumference, intractable epilepsy and growth retardation.He died of persistent convulsions at 4 months.Brain MRI plain scan showed holoprosencephaly, dysplasia of white matter and cerebellum, enlargement of cisterna magna and flat skull base.There were novel compound heterozygous mutations of PNKP gene in the patient, with the heterozygous pathogenic mutation of c.976G > A (p.Glu326Lys) and the unknown clinical significant heterozygous mutation of c.1482C > T (p.Gly494=).His mother had a heterozygous pathogenic mutation of c.976G > A (p.Glu326Lys) and his father carried a unknown clinical significant heterozygous mutation of c.1482C > T (p.Gly494=).Conclusion: The patient is clinically diagnosed as MCSZ and is fatal.There are novel compound heterozygous mutations of PNKP gene in the patient, among which the heterozygous mutation c.1482C > T (p.Gly494=) may be a newly discovered pathogenic mutation.

Key words: microcephaly,seizures and developmental delay, PNKP gene, whole exome sequencing, genetic pedigree