Seckel syndrome and Microcephalic Osteodysplastic Primordial Dwarfistm type II (MOPDII) belong to the microcephalic osteodysplastic dwarfism group characterized by intrauterine growth retardation, dwarfism, and microcephaly. Mutations in PCNT have been identified in patients with Seckel syndrome/MOPDII. Several other genes, including ATR, CENPJ and CEP152 have been reported to cause Seckel syndrome in a small number of families: A homozygous synonymous mutation in ATR [OMIM#601215] has been identified in two consanguineous Pakistani families with Seckel syndrome. ATR is a central player in a signaling response to DNA damage. A homozygous nonsense mutation was identified in CEP63 in a consanguineous family of Pakistani descent with three members with primary microcephaly and proportionate short stature, clinically consistent with mild Seckel syndrome. The CEP63 protein forms a complex with CEP152, and helps to maintain normal centrosome numbers within cells. A homozygous splicing mutation in CENPJ [OMIM#609279] has been identified in a consanguineous Saudi Arabian family with Seckel syndrome. CENPJ is a centrosomal protein and may be involved in microtubule production during mitosis. Homozygous and heterozygous mutations in CEP152 [OMIM#613529] have been identified in Turkish, Italian and South African families with Seckel syndrome. Splicing, frameshift and missense mutations have been reported. CEP152 is a core protein of the centrosome. A homozygous splicing mutation in RBBP8 was identified in four siblings affected by Seckel syndrome in a consanguinous Iraqi family. The RBBP8 protein (also known as CtIP) is involved in the process of DNA double-strand break repair. Mutations in PCNT have been identified in patients with MOPD II/Seckel syndrome. Williams et al (2010) identified 12 homozygous and 1 heterozygous mutation in the PCNT gene in 8/8 patients with MOPDII and 5/16 patients diagnosed with Seckel syndrome. Clinical analysis of Seckel cases with PCNT mutations showed that they all presented with minor skeletal changes and clinical features compatible with a MOPDII diagnosis.
Our Seckel Syndrome Sequencing Panel includes sequence analysis of the following 7 genes: ATR, CENPJ, CEP152, CEP63, NIN, PCNT, RBBP8.
Any gene in the Seckel Syndrome Sequencing Panel can also be ordered individually. Please contact us directly for cost and CPT code information.