Expanding the phenotype of Seckel syndrome associated with biallelic loss-of-function variants in CEP63.

Pekkola Pacheco N, Pettersson M, Lindstrand A, Grigelioniene G

Am. J. Med. Genet. A 191 (7) 1929-1934 [2023-07-00; online 2023-04-05]

Seckel syndrome is an ultrarare autosomal recessive genetically heterogenous condition characterized by intrauterine and postnatal growth restriction, proportionate severe short stature, severe microcephaly, intellectual disability, and distinctive facial features including a prominent nose. Up to now, 40 patients with molecularly confirmed Seckel syndrome have been reported with biallelic variants in nine genes: ATR, CENPJ, CEP63, CEP152, DNA2, NIN, NSMCE2, RBBP8, and TRAIP. Homozygosity for nonsense variant (c.129G>A, p.43*) in CEP63 was described in three cousins with microcephaly, short stature, mild to moderate intellectual disability and diagnoses of Seckel syndrome. Here, we report a second family with three siblings who are compound heterozygous for loss-of-function variants in CEP63, c.1125T>G, p.(Tyr375*) and c.595del, p.(Glu199Asnfs*11). All siblings present with microcephaly, prominent nose, and intellectual disability but only one has severe short stature. Two siblings have aggressive behavior, a feature previously not reported in Seckel syndrome. This report adds two novel truncating variants in CEP63 and extends the clinical knowledge on CEP63-related conditions.

Clinical Genomics Stockholm [Service]

PubMed 37017437

DOI 10.1002/ajmg.a.63200

Crossref 10.1002/ajmg.a.63200

Publications 9.5.0