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[Analysis of D4Z4 mutation in a child with facioscapulohumeral muscular dystrophy presented initially as mental
Yang Tian1, Chi Hou, Zhixiao Yang
1Guangzhou Women and Children's Medical Center, Guangzhou, Guangdong 510000, China. chenwx100@hotmail.com.
Insights
A child with facioscapulohumeral muscular dystrophy (FSHD) and intellectual disability was found to have a D4Z4 copy number variation. This genetic finding may explain both conditions, highlighting a new diagnostic approach for FSHD.
Area of Science:
- Genetics
- Neurology
Background:
- Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder.
- Intellectual disability can be a presenting symptom of FSHD.
Observation:
- A child with FSHD initially presented with significant mental retardation.
- Standard next-generation sequencing (NGS) did not detect pathological mutations.
Findings:
- Molecular combing identified a D4Z4 copy number variation (5.2 kb, 2 copies) in the child, which was de novo.
- The child's IQ was 41, with specific deficits in speech comprehension and perceptual reasoning.
Implications:
- D4Z4 copy number variation is a potential cause of both FSHD and intellectual disability in this case.
- Molecular combing is a valuable tool for diagnosing FSHD by accurately determining D4Z4 repeat numbers.
Objective:
To identify pathological mutation of D4Z4 in a child with facioscapulohumeral muscular dystrophy (FSHD) presented initially as mental retardation.
Methods:
Wechsler Intelligence Scale for Children Revised in China (WISC-IV) was used to assess the patient's IQ. Other clinical data was also collected. With genomic DNA extracted from peripheral blood samples, the child and his parents were subjected to medical exome sequencing and copy number variation analysis by next generation sequencing (NGS). The D4Z4 repeats and their origin source were determined by molecular combing.
Results:
By the WISC-IV test, the child was found to have a total IQ of 41, with a speech comprehension IQ of 45, and perceptual inference index IQ of 52. No pathological mutation was detected by NGS. By molecular combing method, the child was found to carry a D4Z4 spanning 5.2 kb with a copy number of 2. Analysis of his parents indicate that the mutation was de novo.
Conclusion:
The D4Z4 copy number variation may account for the FSHD and mental retardation in the child. The molecular combing method can be used to identify the number of repeat units and facilitate the diagnosis of FSHD.
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