PMC10073441_01
(A) Pictures of the patient: face and profile. No specific dysmorphism is discriminated, but similarities with previous publications are encountered: global facial hypotonia, tented upper lip vermilion, and a low nasal bridge. (B) Weight and height curves of our patient (growth chart:Flanders, 2004, for girls, 1-5 years). Rapid weight gain starting just before 2 years, significant increase between 2 and 3 years of age, and progressive improvement and stabilization of weight related to height at around 4 years of age. (C) Timeline with the main relevant clinical data of the follow-up of our patient.
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F1
Our patient (Figure 1A) is a girl who was initially hospitalized in the context of persistent hypercapnia at 21 months of age. At the same time, she presented with rapid weight gain (Figure 1B). She sat at 2.5 years and walked at 3.5 years (Figure 1C).
2.I Sanger sequencing electropherograms of a novel deletion 8 bp/insertion 10 bp in exon 8 of the P4HTM gene: (A) in the heterozygous state in the healthy mother, (B) in the heterozygous state in the healthy father, and (C) in the homozygous state in the index. Black arrows indicate the start of 8 bp deletion (AGGGAAAC)/10 bp insertion (CACTGTGACA). The red box indicates the 10 bp insertion in Index. 2.II. Moon visualization of the P4HTM gene. (A) Transcript version NM_177939 of P4HTM gene with nine coding exons. (B) The deletion (8 bp)/insertion (10 bp) mutation is located in exon 8 of the transcript. (C) Red arrowheads indicate 8 bp deletion (AGGGAAAC). The green arrowhead indicates 10 bp insertion (CACTGTGACA). (D) The substitution creates a premature stop codon (three codons downstream): NM_177939.3: c.1217_1224delinsCACTGTGACA; NP_808808.1:p.(Lys406Thrfs*3).
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F2
Because of the patient's clinical evolution, at 5 years of age, the whole exome analysis was requested, and a new homozygous pathogenic variant in the P4HTM gene was identified, providing the diagnosis of HIDEA syndrome (Figure 2).