Band-like calcification with simplified gyration and polymicrogyria: report of 10 new families and identification of five novel OCLN mutations.
Band-like calcification with simplified gyration and polymicrogyria (BLC-PMG) is an extremely rare autosomal recessive disorder with distinctive clinical and neuroimaging findings. To date, only 17 patients from 9 unrelated families with BLC-PMG have been reported worldwide. Herein, we describe a series of 13 new patients derived from 10 unrelated Egyptian families. Patients presented at early life with the classic phenotype including severe microcephaly, failure to acquire developmental skills, growth failure and the distinguished calcification patterns involving the cortex, thalami, basal ganglia and pons. Additional features not reported before included calcification of the cerebellum (eight patients: 61.5%) and imperforate anus and undescended testis in a single patient. Molecular studies of the OCLN gene (NM_001205254) identified six distinct candidate mutations. Interestingly, the deletion mutation of the transmembrane domain in exons 3 and 4 (c.51-?_730-?del, p.Lys18_Glu243) was found in five unrelated families (50%), suggesting a founder mutation in our population. On the other hand, five novel truncating mutations (c.809delA (p.K270Rfs*62), c.858_861delTTAT (p.I286Mfs*45), c.1037+5G>C, c.1169C>G (p.S390*) and c.1180delG (p.E394Sfs*91)) were detected, each in one family. To our knowledge, this is the largest series of patients with BLC-PMG. Cerebellum calcification is an additional relevant finding in our series, thus expanding the neuroradiological phenotype of this syndrome.
Division of Human Genetics and Genome Research, Department of Medical Molecular Genetics, National Research Centre, Cairo, Egypt.
Mohamed S
MS
Abdel-Hamid
Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
Ghada M H
GMH
Abdel-Salam
Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
Mahmoud Y
MY
Issa
Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
Bayoumi A
BA
Emam
Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt.
Maha S
MS
Zaki
D000293:Adolescent; D001483:Base Sequence; D002114:Calcinosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D062793:Occludin / Q000235:genetics*; D010375:Pedigree; D065706:Polymicrogyria / Q000000981:diagnostic imaging / Q000235:genetics*; D014057:Tomography, X-Ray Computed; D055815:Young Adult
C568985:OCLN protein, human; D062793:Occludin