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A novel non sense mutation in WDR62 causes autosomal recessive primary microcephaly: a case report
Imane Cherkaoui Jaouad1,2, Abdelali Zrhidri3, Wafaa Jdioui3,4
1Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V, Rabat, Morocco. imane_cj@yahoo.fr.
Background:
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.
Case Presentation:
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.
Conclusion:
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.
Insights
Primary microcephaly (MCPH) is a rare brain development disorder. Whole-exome sequencing identified a novel WDR62 gene mutation in two patients, aiding diagnosis and genetic counseling.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Autosomal recessive primary microcephaly (MCPH) is a rare, genetically heterogeneous neurodevelopmental disorder.
- Characterized by reduced head circumference at birth without significant brain architecture anomalies.
- Genetic heterogeneity presents a major challenge for diagnosing MCPH.
Observation:
- Two siblings with MCPH, born to consanguineous parents, underwent whole-exome sequencing.
- A novel homozygous mutation (c.1027C>T; p.Gln343*) in the WDR62 gene was identified in exon 8.
- Sanger sequencing confirmed the mutation's segregation within the family.
Findings:
- The identified mutation expands the known spectrum of WDR62 gene mutations associated with MCPH.
- Whole-exome sequencing proved efficient and cost-effective for diagnosing this genetically heterogeneous disorder.
- Rapid identification of the novel mutation facilitated timely genetic counseling.
Implications:
- Highlights the utility of whole-exome sequencing in diagnosing rare genetic disorders.
- Contributes to understanding the genetic basis of primary microcephaly.
- Enables more accurate genetic counseling and family planning for affected individuals.
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