Barth syndrome (BTHS) is an X-linked genetic condition, usually transmitted from mother to son (although there is a relatively high incidence of new mutations in Barth syndrome and one confirmed case report of a female Barth syndrome patient). A mother who is a carrier of a Barth syndrome mutation (the gene is named tafazzin — also called TAZ or G4.5) shows no signs or symptoms of this disorder herself, probably due to skewed X-chromosome inactivation.
There is a 50% chance that a boy born to a female carrier will have Barth syndrome, whereas girls born to a carrier have a 50% risk of being carriers themselves. All daughters of a male with Barth syndrome will be carriers, however no sons will be affected. Because there are proven non-carrier mothers, all mothers of Barth syndrome children should be tested in order to define the genetic risk in each family.
Any male child related through the female line to a Barth syndrome individual should be tested for the disorder, as there can be great variation in phenotype even among affected siblings.
Female carriers of Barth syndrome are healthy. This has been associated with X chromosome inactivation [Orstavik et al. (1998)], using PCR of a polymorphic CAG repeat in the first exon of the androgen receptor gene (AR; 313700). Although it is theoretically possible for a female who carries a mutation in the Barth gene to have clinical signs of the disorder, as yet there has been no proven affected female with a normal 46,XX female karyotype.
(Follow link to view What's in Your Genes presentation)
The Female Side of Barth - Calling All Adult Women
What is this research study? As more boys and men are correctly diagnosed with Barth syndrome, mothers, sisters, daughters, and grandmothers face their own challenges. This questionnaire study builds on interviews we did with Barth Syndrome carriers to measure the emotional, family, reproductive, and psychological implications of having a relative with Barth syndrome. We are asking ALL ADULT WOMEN to join. We hope study results will help both health care providers and patient organizations provide better care to women in families with X-linked conditions, especially Barth syndrome!
Study Principal Investigator: Cynthia James / Study Genetic Counselor: Rebecca McClellan
BSF 8th International Scientific, Medical & Family Conference
July 18-23, 2016 ~ Clearwater Beach, FL
From DNA to TAZ variants ...is this a mutation or not?
Iris L. Gonzalez, PhD — A. I. duPont Hospital for Children, Wilmington, DE, USA
Tips and strategies for talking to your children about genetics
Rebecca L. McClellan, MGC, CGC — Kennedy Krieger Institute, Baltimore, MD; Cynthia James, ScM, PhD — Johns Hopkins University, Baltimore, MD; Lee Kugelmann, Co-Lead, Carrier Program, Barth Syndrome Foundation
Study update: How do women adapt to being a Barth syndrome carrier?
Rebecca L. McClellan, MGC, CGC — Kennedy Krieger Institute, Baltimore, MD; Cynthia James, ScM, PhD — Johns Hopkins University, Baltimore, MD
What we have learned, where to go from here, and how you can get involved?
Lee Kugelmann, Co-Lead, Carrier Program, Barth Syndrome Foundation