Abstract
We describe a 16-year-old boy with an 8.6Mb interstitial deletion of chromosome 4q 13.3q21.23 identified by oligo array-CGH. The patient presents psychomotor developmental delay, absent speech, marked progressive growth restriction, hearing loss, skeletal defects and minor facial anomalies. The patient required surgical treatment for cleft lip and palate, bilateral cryptorchidism and a neurofibroma. The analysis of the presented patient against previously published cases allowed us to expand further on the phenotype and to reevaluate previously proposed critical overlapping region at 4q21. As an addition to PRKG2 and RASGEFIB genes, we propose to include BMP3 gene as the principal determinant of the observed common phenotype. BMP3 haploinsufficiency appears to be causative of hearing loss and peculiar skeletal abnormalities including hemivertebrae and brachydactyly.
MeSH terms
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Abnormalities, Multiple / diagnosis
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Abnormalities, Multiple / genetics*
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Adolescent
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Alleles
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Bone Morphogenetic Protein 3 / genetics*
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Chromosome Deletion*
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Chromosomes, Human, Pair 4 / genetics*
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Cleft Lip / diagnosis
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Cleft Lip / genetics
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Cleft Palate / diagnosis
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Cleft Palate / genetics
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Cyclic GMP-Dependent Protein Kinase Type II
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Cyclic GMP-Dependent Protein Kinases / genetics*
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DNA Copy Number Variations
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Growth Disorders / diagnosis
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Growth Disorders / genetics*
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Hearing Loss, Sensorineural / diagnosis
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Hearing Loss, Sensorineural / genetics*
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Humans
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Intellectual Disability / diagnosis
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Intellectual Disability / genetics*
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Male
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Oligonucleotide Array Sequence Analysis
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Phenotype
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Real-Time Polymerase Chain Reaction
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ras Guanine Nucleotide Exchange Factors / genetics*
Substances
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BMP3 protein, human
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Bone Morphogenetic Protein 3
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RasGEF1B protein, human
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ras Guanine Nucleotide Exchange Factors
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Cyclic GMP-Dependent Protein Kinase Type II
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Cyclic GMP-Dependent Protein Kinases
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PRKG2 protein, human
Supplementary concepts
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Pfeiffer Kapferer syndrome