A novel non sense mutation in WDR62 causes autosomal recessive primary microcephaly: a case report

• Published in: BMC medical genetics Vol. 19; no. 1; p. 118
• Main Authors: Cherkaoui Jaouad, Imane, Zrhidri, Abdelali, Jdioui, Wafaa, Lyahyai, Jaber, Raymond, Laure, Egéa, Grégory, Taoudi, Mohamed, El Mouatassim, Said, Sefiani, Abdelaziz
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18-07-2018; BioMed Central; BMC
• Subjects: Autosomal recessive primary microcephaly; Birth weight; Brain; Brain - abnormalities; Brain architecture; Care and treatment; Case Report; Case reports; Case studies; Child; Chromosome abnormalities; Deoxyribonucleic acid; Diagnosis; DNA; Female; Genetic counseling; Genetic disorders; Genetic heterogeneity; Genomes; Homozygote; Humans; Intellectual disabilities; Male; Microcephaly; Microcephaly - genetics; Mutation; Mutation - genetics; Nerve Tissue Proteins - genetics; Parents & parenting; Patients; Pedigree; Software; WDR62; Whole exome sequencing; Morocco; Autosomal recessive primary microcephaly; WDR62; Whole exome sequencing; Genetic heterogeneity
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-018-0625-6

Autosomal recessive primary microcephaly (MCPH) is a rare genetically heterogeneous disorder of neurogenic brain development characterized by a reduced head circumference at birth with no remarkable anomalies of brain architecture and variable degrees of intellectual impairment. Clinical and genetic heterogeneity in genetic disorders represent a major diagnostic challenge.
Two patients, 11 and 9 years old, born from consanguineous parents, were referred to the department of medical genetics at the National Institute of Health in Rabat. The diagnosis of MCPH was made, based on reduced head circumference without brain architecture abnormalities. The two patients were subject to the whole-exome sequencing, which allowed to diagnose a novel homozygous mutation c.1027C > T; p.Gln343* in exon 8 of WDR62, a gene already known to be related to MCPH. Sanger sequencing confirmed the segregation of the mutation in the family.
Our data expends the spectrum of mutations in WDR62 gene, proves the efficiency and cost-effectiveness of whole exome sequencing for the molecular diagnosis of genetically heterogeneous disorders such MCPH. Exome sequencing led to the rapid and cost-effective identification of a novel homozygous mutation in WDR62 gene, thereby facilitating genetic counseling.