Neonatal McCune-Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome.

Somatic gain-of-function mutations of GNAS cause a spectrum of clinical phenotypes, ranging from McCune-Albright syndrome (MAS) to isolated disease of bone, endocrine glands, and more rarely, other organs. In MAS, a syndrome classically characterized by polyostotic fibrous dysplasia (FD), café-au-lait (CAL) skin spots, and precocious puberty, the heterogenity of organ involvement, age of onset, and clinical severity of the disease are thought to reflect the variable size and the random distribution of the mutated cell clone arising from the postzygotic mutation. We report a case of neonatal MAS with hypercortisolism and cholestatic hepatobiliary dysfunction in which bone changes indirectly emanating from the disease genotype, and distinct from FD, led to a fatal outcome. Pulmonary embolism of marrow and bone fragments secondary to rib fractures was the immediate cause of death. Ribs, and all other skeletal segments, were free of changes of typical FD and fractures appeared to be the result of a mild-to-moderate degree of osteopenia. The mutated allele was abundant in the adrenal glands and liver, but not in skin, muscle, and fractured ribs, where it could only be demonstrated using a much more sensitive PNA hybridization probe-based FRET (Förster resonance energy transfer) technique. Histologically, bilateral adrenal hyperplasia and cholestatic disease matched the abundant disease genotype in the adrenals and liver. Based on this case and other sporadic reports, it appears that gain-of-function mutations of GNAS underlie a unique syndromic profile in neonates characterized by CAL skin spots, hypercortisolism, hyperthyroidism, hepatic and cardiac dysfunction, and an absence (or latency) of FD, often with a lethal outcome. Taken together, our and previous cases highlight the phenotypic severity and the diagnostic and therapeutic challenges of MAS in neonates. Furthermore, our case specifically points out how secondary bone changes, unrelated to the direct impact of the mutation, may contribute to the unfavorable outcome of very early-onset MAS.

Relationships and the development of transition readiness skills into early emerging adulthood for individuals with type 1 diabetes.

The study examined how 'transition readiness' skills develop from relationship processes with parents, friends, and healthcare providers. During their senior year of high school and one year later, participants (N = 217) with type 1 diabetes completed measures of transition readiness skills (Self-Management; Self-Advocacy), adherence, HbA1c, and relationships with providers (patient-centered communication), parents (monitoring/knowledge), and friends (knowledge/helpfulness) surrounding diabetes. Self-Management skills increased across time. Higher friend knowledge/helpfulness during emerging adulthood was associated with increased Self-Management skills. Adherence improved when relationships with providers and friends matched transition readiness skills, indicating that these relationships may facilitate transition skills in early emerging adulthood.

Screening method for isopeptides from small ubiquitin-related modifier-conjugated proteins by ion mobility mass spectrometry.

Posttranslational modification by the small ubiquitin-related modifier (SUMO) is a highly regulated modification, which is often restricted to very specific cellular events. A number of analytical strategies for identification of SUMOylated proteins have been previously reported in the literature. A new screening method for SUMOylated peptides based on ion mobility mass spectrometry is presented. Using poly-SUMO2 as a model system, a two-enzyme trypsin/chymotrypsin digestion was performed to reduce the size of the isopeptide conjugated to the substrate lysine residue. Traveling wave ion mobility mass spectrometry was used to screen for peptides containing the QQQTGG isopeptide tag from SUMO, which increases the mass and size of the peptide by 618 Da. This increase in mass along with solution conditions to promote higher charge states allows the isopeptides to be separated from the typically smaller and lesser charged linear peptides. On the basis of these findings, this method can be used as a quick and easy screening method for identifying possible SUMO isopeptides.

Mother child appraised involvement in coping with diabetes stressors and emotional adjustment.

OBJECTIVE: To examine how children's and mother's appraisals of each other's involvement in coping with diabetes events are associated with emotional adjustment. METHODS: One hundred and twenty-seven children (ages 10-15 years) with type 1 diabetes and their mothers reported on their own emotional adjustment and how each other was involved in coping strategies surrounding diabetes stressful events. RESULTS: Appraisals that mothers and children were uninvolved with each other's stressors were associated with greater depressive symptoms and less positive mood; children's appraisals of mother's supportive involvement with children's less depressive symptoms, and appraisals of collaborative involvement with less depressive symptoms and more positive mood for both mothers and children. Appraised control was most detrimental for children for older females and for mothers of younger children. CONCLUSIONS: Collaborative involvement in coping efforts may be an important resource for addressing negative emotions that both children and mothers experience surrounding type 1 diabetes, especially across adolescence.

Children's appraisals of maternal involvement in coping with diabetes: enhancing our understanding of adherence, metabolic control, and quality of life across adolescence.

OBJECTIVE: To examine how children's appraisals of maternal involvement in coping with diabetes are associated with adherence, metabolic control, and quality of life across adolescence. METHODS: Children (N = 127, ages 10-15 years) with type 1 diabetes completed measures of adherence, quality of life, and appraisals of mothers' involvement in dealing with diabetes problems (i.e., mother appraised as uninvolved, controlling, or collaborative). Metabolic control was indexed through medical records. RESULTS: Regardless of age or sex of child, appraised maternal uninvolvement was associated with poorer adherence and quality of life, while appraised collaboration was associated with better adherence and metabolic control. There was evidence that the association between appraised collaboration and metabolic control was partially mediated by adherence. Appraised control was associated with poorer adherence among older, but not younger, children and with poorer quality of life among older females but not among older males or younger children of either sex. CONCLUSIONS: Maintaining maternal involvement in diabetes care is important across ages 10 to 15, but the optimal form of this involvement may need to be adjusted to be consistent with the child's level of development. The present findings suggest that better adherence is seen across age when mothers are viewed as collaborating with, as opposed to controlling, their child when dealing with diabetes problems.

The role of autonomy and pubertal status in understanding age differences in maternal involvement in diabetes responsibility across adolescence.

OBJECTIVE: To examine how autonomy and pubertal status explain age decreases in maternal involvement in type 1 diabetes management across adolescence, how they relate to metabolic control, and the reasons that guide declines in maternal involvement. METHODS: One hundred twenty-seven children ages 10-15 years with type 1 diabetes and their mothers participated. Data included maternal and child report of diabetes management, child report of autonomy level, maternal report of pubertal status, maternal reports of reasons for transfer of diabetes responsibility, and glycosylated hemoglobin (Hba(1c)) values. RESULTS: Autonomy and pubertal status partially mediated age effects on reports of maternal involvement. Mothers' reasons for transferring responsibility included responding to the child's competence, promoting competence and maturity in their child, and minimizing hassles and conflict. The transfer of diabetes responsibility from mother to child without sufficient autonomy and when pubertal status was low was related to higher Hba(1c) values. CONCLUSIONS: The importance of chronological age for changes in maternal involvement suggests the need to examine mothers' and adolescents' developmental expectations for diabetes management. The reasons for transferring responsibility from mother to child suggest many avenues for intervention.

Prenatal diagnosis of 21-hydroxylase deficiency caused by gene conversion and rearrangements: pitfalls and molecular diagnostic solutions.

OBJECTIVES: The present paper reports the prenatal diagnosis of congenital adrenal hyperplasia (CAH) in two cases of 21-hydroxylase deficiency. DNA diagnostic errors can be caused by the presence of the highly homologous 21-hydroxylase pseudogene, CYP21P, adjacent to the functional gene, CYP21. The present paper details how complex gene conversions and rearrangements between the CYP21 and CYP21P pose unique complications for prenatal diagnosis. METHODS: Analysis of eight common mutations in the 21-hydroxylase gene as well as deletion of the entire gene is accomplished using polymerase chin reaction (PCR) followed by amplified created restriction site (ACRS) or allele-specific oligohybridization (ASO) and Southern blot followed by hybridization to a CYP21-specific probe. Linkage analysis was performed using microsatellite markers flanking the CYP21 gene. RESULTS: The direct mutation detection assay indicated a complicated gene conversion and rearrangement in the probands of both families. Interpretation of these rearrangements made it difficult to determine whether or not the fetuses would be affected with CAH. Linkage studies revealed that each fetus had inherited both parental disease chromosomes and was therefore predicted to be affected with CAH. CONCLUSION: As observed in the two reported cases, direct DNA analysis may provide limited information due to gene conversion or rearrangement between the CYP21 and CYP21P genes. These cases suggest that direct mutation detection should be supported by linkage analysis, whenever possible, to provide more comprehensive information for the family.