Mary E. Carlin

HERV-Mediated Genomic Rearrangement of EYA1 in an Individual With Branchio-oto-renal Syndrome

Branchio‐oto‐renal syndrome is characterized by branchial defects, hearing loss, preauricular pits, and renal anomalies. Mutations in EYA1 are the most common cause of branchio‐oto‐renal and branchio‐otic syndromes. Large chromosomal aberrations of 8q13, including complex rearrangements occur in about 20% of these individuals. However, submicroscopic deletions and the molecular characterization of genomic rearrangements involving the EYA1 gene have rarely been reported. Using the array‐comparative genomic hybridization, we identified non‐recurrent genomic deletions including the EYA1 gene in three patients with branchio‐oto‐renal syndrome, short stature, and developmental delay. One of these deletions was mediated by two human endogenous retroviral sequence blocks, analogous to the AZFa microdeletion on Yq11, responsible for male infertility. This report describes the expanded phenotype of individuals, resulting from contiguous gene deletion involving the EYA1 gene and provides a molecular description of the genomic rearrangements involving this gene in branchio‐oto‐renal syndrome.

Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27

Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype–phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.

Heterogeneity in Wiedemann-Beckwith syndrome: Anthropometric evidence

Wiedemann-Beckwith syndrome (WBS) has attracted a great deal of attention because of its genetic complexity. Individuals with WBS can be identified objectively by anthropometric analysis. Craniofacial anthropometry in conjunction with multivariate statistical analysis can be used to define patterns of variability that appear to relate to specific modes of inheritance that have been proposed for WBS. Our data on 19 affected individuals and their first-degree relatives indicate that the pattern of inheritance rather than the age of subjects may be responsible for the highly variable craniofacial phenotype found in individuals diagnosed with WBS.

Prenatal diagnosis of a de novo trisomy 6q22.2→6qter and monosomy lpter→1p36.3. Case report with a 2‐year follow‐up and a brief review of other prenatal cases of partial trisomy 6q

We report a de novo trisomy 6q22.2→6qter and monosomy lpter→1p36.3 identified in amniocytes by GTG banding and FISH. While ultrasonography demonstrated malformations that did not suggest a specific chromosomal syndrome, a male infant with features consistent with trisomy 6q was born. He was followed up until 23 months, when he died after cardiac surgery. The only two other prenatal cases of trisomy 6q were compared with our patient. A literature review showed that trisomy 6q has not been reported in association with the anomalies seen by ultrasound in this case.

Granulomatous lung disease with progressive deterioration of phagocytic function

A 3-year-old girl is described who had laboratory and histopathologic features which placed her within the spectrum of chronic granulomatous disease of childhood. Her illness differed from that of previously described patients with phagocytic dysfunction syndromes in that her leukocyte nitroblue tetrazolium values progressively decreased over the period of observation, and depression of cell-mediated immunity was identified by several parameters.