PMC7575812_01
PMC7575812_02
Dysmorphic features of our patient. Dolichocephaly, bossing forehead, dysmorphic low set ears (A), facial dysmorphism (B), bilateral inverted nipples (C), abnormal fat distribution (D,E), and hammertoes (F).
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F1
His dysmorphic features included dolichocephaly, bossing forehead, dysmorphic low set ears (Figure 1A), enlarged fontanelle, wider philtrum, broad nasal root, prominent nares, hypertelorism, retrognathia (Figure 1B), inverted nipples (Figure 1C), abnormal fat distribution over his thighs, buttocks and suprapubic regions (Figure 1D,E), pilonidal sinus and hammertoes (Figure 1F).
PMC7575812_03
Results of the DNA and RNA sequencing. Molecular analysis presenting variant c.691G > A/p.Val231Met (A) and variant c.447 + 3dupA in the PMM2 gene (B) in the patient's DNA from exome sequencing in Integrative Genomics Viewer (IGV) and Sanger sequencing analysis (bottom part). At RNA level, over 70% of mRNA was produced from c.691A > G allele (C) and the proportion of exon five skipping was over 30% of all transcripts (D).
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F2
As it was expected, results confirmed both variants in the proband and showed that c.691G > A/p.Val231Met variant was inherited from father (Figure 2A) and c.447 + 3dupA variant from mother (Figure 2B), presenting the typical autosomal recessive mode of inheritance. We have confirmed that c. 447 + 3dupA variant causes a loss of donor splice site, leads to exon five skipping (r.348_447del100), and causes premature termination of translation and protein truncation (p.G117Kfs*4; Figure 2C,D), and therefore, it can be classified as a class 4:likely pathogenic.
PMC7575812_04
Transthoracic echocardiogram (4-chamber view) showing a large pericardial effusion in our patient.
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F3
Pericardial effusion further progressed (Figure 3) and finally required pericardiocentesis.