Table 1 Main findings in the 9 Chinese patients and our case
Reference | Total cases | Sex, Age onset | ZFYVE19 gene mutations | First clinical features | Clinical evolution | Hystopathologic features | Renal cystic change | ↑GGT ↑GPT ↑GOT | Outcome | Ciliary studies | |
|---|---|---|---|---|---|---|---|---|---|---|---|
Nucleotide change | Aminoacid change | ||||||||||
Luan et al. (2020) | 9 | M, birth | c.314C > G | p.S105X | Neonatal jaundice | Resolved Jaundice, 8 months. Hepato-splenomegaly. UGIH | Explanted liver, micronodular cirrhosis, ductular reaction | No | Yes | LT at 5 y 6 m | In ZFYVE19-knockdown hRPE1 cells, a prominent phenotypical abnormality, was an increase in numbers of basal bodies/centrioles. Separation/abnormal arrangement of the centriole pair(s) was also observed. However, cilium assembly was not affected and extra cilia took shape at extra basal bodies/ centrioles In ZFYVE19-deficient fibroblast-like cells derived from patient iPSCs, similar phenotypes involving abnormalities of ciliary and centriolar numbers but not of cilium assembly were demonstrated In both cells: supernumerary centrioles and cilia when ZFYVE19 was depleted |
Sisters F, 5 y | c.226A > G c.314C > G | p.M76V p.S105X | Hepato-splenomegaly. Portal hypertension | DPM | No | Yes | Improved LFTs on UDCA at 15 y worsened on UDCA at 17 y | ||||
F, 14 m | Hepatomegaly | Hepatomegaly | No | Yes | Improved LFTs on UDCA at 10 y 4 m; UDCA stopped at 12 y 4 m | ||||||
M, 40 days | c.314C > G c.514C > T | p.S105X p.R172X | Neonatal jaundice, diarrhoea | Pruritus. Hepato-splenomegaly. Portal hypertension | DPM | No | Yes | Improved LFTs on UDCA at 14 y 1 m | |||
M, 4 m | c.314C > G | p.S105X | Fever, diarrhea | Hepato-splenomegaly. Portal hypertension. UGIH | DPM, cholestasis | No | Yes | LT at 6 y 4 m | |||
M, 3 m | c.547C > T c.314C > G | p.R183X p.S105X | Neonatal jaundice | Hepato-splenomegaly | Portal widening and fibrosis, ductular reaction | No | Yes | Normalised LFTs on UDCA at 6 y | |||
Sisters F, 9 y | c.514C > T | p.R172X | Hepato-splenomegaly | Hepato-splenomegaly | DPM | No | Yes | Improved LFTs on UDCA at 11 y | |||
F, 4 y | UGIH | DPM, fibro-obliterative loss of bile ducts with DPM | No | Yes | LT at 4 y 8 m | ||||||
M, 3 m | c.379C > T c.314C > G | p.Q127X p.S105X | Neonatal jaundice Fever, cough | Hepato-splenomegaly. Portal hypertension. UGIH | DPM, fibro-obliterative loss of bile ducts with DPM, cholestasis | No | Yes | LT at 1 y 10 m | |||
Present case | 1 | F, 59 days | c.667C > T | p.R223X [p.Arg223Ter] | Cholestatic jaundice. Hepato-splenomegaly | Hepato-splenomegaly Anicteric cholestasis | Micronodular cirrhosis, bile ducts proliferation and portal tract abnormalities consonant with DPM or CHF | No | Yes | Mild ↑ LFTs, persistent anicteric cholestasis with preserved protein synthesis, on UDCA and Rifampicin (5y) | Immunofluorescence analysis of primary cilia on cultured skin fibroblasts showed fragmented cilia and centrioles abnormalities |