Graphical representation of the categories and subcategories identified in the forms. ^†Value includes 13 forms that did not mention unsolicited findings (UF) and/or secondary findings (SF).

A French-Canadian founder mutation in GBA, p.Trp378Gly, is located between the enzyme active site and the binding area of Saposin C. This mutation causes Gaucher disease in compound heterozygous carriers, with or without Parkinson disease, and is a risk factor for synucleinopathies in heterozygous carriers.

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) (OMIM #617481) is an autosomal recessive disease characterized by progressive microcephaly, plagiocephaly, hypotonia, spastic quadriparesis, global developmental delay, intellectual disability, optic features and abnormal brain magnetic resonance imaging (MRI). NMIHBA was recently reported to be caused by PRUNE1 mutations. Here, we report 3 PRUNE1 mutations in 1 Caucasian and 3 Japanese families. The patients presented in this study showed atypical NMIHBA phenotypes with no progressive microcephaly. Furthermore, one Caucasian case had significant macrocephaly; therefore, patients with PRUNE1 mutations can exhibit a broad and heterogeneous spectrum of phenotypes.

Novel IFT80 mutations (Lys408Glu and Lys306*) were identified in a patient with none of the features of Jeune syndrome (normal chest and pelvic x-rays) but retinal degeneration and a phenotype otherwise reminiscent of OFD6 (molar tooth sight, brain hamartoma digit anomaly). The amino acids involved were highly conserved and predicted to lead to the loss of most on the C-terminal domain on protein modeling. This expands the phenotype spectrum associated with IFT80 mutations.

By describing 10 new patients recruited in centers for Human Genetics, we further delineate the clinical spectrum of a Crouzon-like craniosynostosis disorder, officially termed craniosynostosis and dental anomalies (MIM614188). Singularly, it is inherited according to an autosomal recessive mode of inheritance. We identified six missense mutations in IL11RA, a gene encoding the alpha subunit of interleukin 11 receptor, 4 of them being novel, including 2 in the Ig-like C2-type domain.

LAMB1 gene analysis should be considered for intellectually disabled patients with cerebellar cysts, white matter signal change, and cortical malformation. Muscular involvement is absent, in contrast to the α-dystroglycanopathy types of congenital muscular dystrophies.

We identified the homozygous p.Arg12* variant in 5 patients with neurodevelopmental delay, but variation databases list many truncating heterozygous variants for this small 2-exon gene. As most of these affect the protein’s C-terminus, loss-of-function mediated pathogenicity may be confined to bi-allelic truncating variants in exon 1 (nonsense-mediated decay!) or in the catalytically active Nudix box.