Matches in SemOpenAlex for { <https://semopenalex.org/work/W2142929373> ?p ?o ?g. }
- W2142929373 endingPage "398" @default.
- W2142929373 startingPage "389" @default.
- W2142929373 abstract "<h3>Background:</h3> Holoprosencephaly (HPE) is the most common structural malformation of the human forebrain. There are several important HPE mutational target genes, including the transcription factor <i>SIX3</i>, which encodes an early regulator of Shh, Wnt, Bmp and Nodal signalling expressed in the developing forebrain and eyes of all vertebrates. <h3>Objective:</h3> To characterise genetic and clinical findings in patients with <i>SIX3</i> mutations. <h3>Methods:</h3> Patients with HPE and their family members were tested for mutations in HPE-associated genes and the genetic and clinical findings, including those for additional cases found in the literature, were analysed. The results were correlated with a mutation-specific functional assay in zebrafish. <h3>Results:</h3> In a cohort of patients (n = 800) with HPE, <i>SIX3</i> mutations were found in 4.7% of probands and additional cases were found through testing of relatives. In total, 138 cases of HPE were identified, 59 of whom had not previously been clinically presented. Mutations in <i>SIX3</i> result in more severe HPE than in other cases of non-chromosomal, non-syndromic HPE. An over-representation of severe HPE was found in patients whose mutations confer greater loss of function, as measured by the functional zebrafish assay. The gender ratio in this combined set of patients was 1.5:1 (F:M) and maternal inheritance was almost twice as common as paternal. About 14% of <i>SIX3</i> mutations in probands occur de novo. There is a wide intrafamilial clinical range of features and classical penetrance is estimated to be at least 62%. <h3>Conclusions:</h3> Our data suggest that <i>SIX3</i> mutations result in relatively severe HPE and that there is a genotype–phenotype correlation, as shown by functional studies using animal models." @default.
- W2142929373 created "2016-06-24" @default.
- W2142929373 creator A5004227153 @default.
- W2142929373 creator A5008262289 @default.
- W2142929373 creator A5011636981 @default.
- W2142929373 creator A5012146929 @default.
- W2142929373 creator A5012216196 @default.
- W2142929373 creator A5014185321 @default.
- W2142929373 creator A5020340477 @default.
- W2142929373 creator A5022334514 @default.
- W2142929373 creator A5023846300 @default.
- W2142929373 creator A5030485933 @default.
- W2142929373 creator A5030746443 @default.
- W2142929373 creator A5031663338 @default.
- W2142929373 creator A5032719767 @default.
- W2142929373 creator A5035331197 @default.
- W2142929373 creator A5035778305 @default.
- W2142929373 creator A5037050823 @default.
- W2142929373 creator A5037249701 @default.
- W2142929373 creator A5038583289 @default.
- W2142929373 creator A5039907535 @default.
- W2142929373 creator A5040920280 @default.
- W2142929373 creator A5041576364 @default.
- W2142929373 creator A5042183876 @default.
- W2142929373 creator A5043373212 @default.
- W2142929373 creator A5048874172 @default.
- W2142929373 creator A5050648441 @default.
- W2142929373 creator A5050807433 @default.
- W2142929373 creator A5054516309 @default.
- W2142929373 creator A5055868133 @default.
- W2142929373 creator A5056134155 @default.
- W2142929373 creator A5056289146 @default.
- W2142929373 creator A5056744774 @default.
- W2142929373 creator A5057619639 @default.
- W2142929373 creator A5064145843 @default.
- W2142929373 creator A5064982358 @default.
- W2142929373 creator A5067442385 @default.
- W2142929373 creator A5072288662 @default.
- W2142929373 creator A5076541018 @default.
- W2142929373 creator A5076632414 @default.
- W2142929373 creator A5078501682 @default.
- W2142929373 creator A5079710467 @default.
- W2142929373 creator A5081715355 @default.
- W2142929373 creator A5082240858 @default.
- W2142929373 creator A5083652731 @default.
- W2142929373 creator A5086473001 @default.
- W2142929373 creator A5089060602 @default.
- W2142929373 creator A5089771046 @default.
- W2142929373 date "2009-04-02" @default.
- W2142929373 modified "2023-10-17" @default.
- W2142929373 title "Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function" @default.
- W2142929373 cites W1493790738 @default.
- W2142929373 cites W1570966949 @default.
- W2142929373 cites W1573159729 @default.
- W2142929373 cites W1744074667 @default.
- W2142929373 cites W1759401885 @default.
- W2142929373 cites W1963573559 @default.
- W2142929373 cites W1966435498 @default.
- W2142929373 cites W1969066254 @default.
- W2142929373 cites W1972001067 @default.
- W2142929373 cites W1973012722 @default.
- W2142929373 cites W1975928478 @default.
- W2142929373 cites W1990822370 @default.
- W2142929373 cites W1994452395 @default.
- W2142929373 cites W1999762161 @default.
- W2142929373 cites W2001036127 @default.
- W2142929373 cites W2011231507 @default.
- W2142929373 cites W2017286027 @default.
- W2142929373 cites W2018721216 @default.
- W2142929373 cites W2022753721 @default.
- W2142929373 cites W2023501279 @default.
- W2142929373 cites W2029150089 @default.
- W2142929373 cites W2046494933 @default.
- W2142929373 cites W2051199478 @default.
- W2142929373 cites W2056683774 @default.
- W2142929373 cites W2057980992 @default.
- W2142929373 cites W2062684623 @default.
- W2142929373 cites W2064362618 @default.
- W2142929373 cites W2072151865 @default.
- W2142929373 cites W2075841184 @default.
- W2142929373 cites W2077557270 @default.
- W2142929373 cites W2080030928 @default.
- W2142929373 cites W2083467596 @default.
- W2142929373 cites W2086535617 @default.
- W2142929373 cites W2104687889 @default.
- W2142929373 cites W2111712057 @default.
- W2142929373 cites W2112108010 @default.
- W2142929373 cites W2112388671 @default.
- W2142929373 cites W2113815624 @default.
- W2142929373 cites W2128736049 @default.
- W2142929373 cites W2132549779 @default.
- W2142929373 cites W2141713989 @default.
- W2142929373 cites W2144414226 @default.
- W2142929373 cites W2145636711 @default.
- W2142929373 cites W2146111983 @default.
- W2142929373 cites W2147804736 @default.
- W2142929373 cites W2148226412 @default.
- W2142929373 cites W2152463585 @default.