PMC8523853_01
Phenotypes of ciliary diseases {Family 1 [(A): case 1; (B,C): case 2], Family 4 [(D): case 6], Family 5 [(E,F): case 8], occipital encephalocele (C), polydactyly of hands and feet (D-F), short limb and ribs (D,E)}.
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F1
The pregnancy was subsequently terminated at the 18th week of gestation (Figure 1D). Examination of the aborted fetus showed low-set ears, polydactyly, a swollen abdomen, and short limbs (Figures 1E,F).
Imaging examination of ciliary diseases {Family 1 [(A): case 2], Family 3 [(B): case 5], Family 4 [(C): case 6], Family 5 [(D): case 8], occipital encephalocele (A), increased echogenicity in both renal cortexes (B), fetal X-ray showing bilateral shortened curved femora and disproportionately shortened tibiae (C), bone dysplasia and narrow chest (D)}.
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F2
Fetal X-ray (Figure 2C) showed bilateral shortened curved femora and disproportionately shortened tibiae. Besides, increased bowel and kidney echo, and bone dysplasia (femur = 1.3 cm, humerus = 0.9 cm, narrow chest) (Figure 2D) were detected.
Missense variants of the TMEM67 gene in MKS and JBS. There were about 58 (likely) pathogenic missense variants in the TMEM67 gene identified thus far including 37 in JBS (green), 15 in MKS (red), and 6 in both (blue). The topology of TMEM67: a signal peptide (1-36 aa), a cysteine-rich region (50-187 aa), an extracellular area with unknown structure (188-526 aa), seven transmembrane regions (527-967 aa), and a short cytoplasmic tail (968-995 aa).
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F3
Analysis of the topology of human TMEM67 suggests the presence of a signal peptide (1-36 aa), a cysteine-rich region (50-187 aa), an extracellular area with unknown structure (188-526 aa), seven transmembrane regions (527-967 aa), and a short cytoplasmic tail (968-995 aa) (Figure 3). Pathogenic missense variants of TMEM67 mainly fall in the extracellular cysteine rich region, extracellular area with unknown structure, and the seven transmembrane regions (Figure 3). No pathogenic missense variant in the signal peptide and cytoplasmic tail has been reported (Figure 3).