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| Prepair 1000+ v1.592 | GCH1 | Lilian Downie Added comment: Comment when marking as ready: Biallelic variants in GCH1 typically result in severe deficiency of GTPCH activity, and result in hyperphenylalaninemia due to secondary PAH deficiency. This can be identified by newborn screening. However, patients with phenotypes that are intermediate between the classic DRD and severe GTPCH deficiency symptoms have been described, such those with severe DRD and additional neurological features but without hyperphenylalaninemia (for review, see Table in Brüggemann et al 2012, PMID 22473768). Because the mechanism of disease in both the monoallelic and biallelic cases is loss of function of GTPCH, and there is a range of GTPCH activity that can cause disease, the decision was made to curate GCH1 for GTPCH deficiency with semi-dominant inheritance. Note that heterozygous parents of biallelic individuals are usually reported as unaffected, although there are some exceptions (Furukawa et al, 1998, PMID 9667588; Bodzioch et al, 2010, PMID 20842687). Reduced penetrance has been reported for individuals with monoallelic GCH1 variants, with penetrance varying according to age and diagnostic criteria. In addition, some variants (e.g. p.Arg184His and p.Lys224Arg) have been reported in monallelic and biallelic individuals. This data was presented to the ClinGen Lumping and Splitting Working Group on November 3, 2020 and there was agreement that GTPCH deficiency should be curated as a semi-dominant trait, including individuals with monoallelic and biallelic GCH1 variants. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v1.3 | PAH | Seb Lunke Added phenotypes Phenylketonuria, 261600 (3) for gene: PAH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Prepair 1000+ v0.0 | PAH |
Zornitza Stark gene: PAH was added gene: PAH was added to Reproductive Carrier Screen_VCGS. Sources: Mackenzie's Mission,Expert Review Green Mode of inheritance for gene: PAH was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PAH were set to Phenylketonuria, 261600 (3) |
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