RESEARCH LETTER
Ataxia-Telangiectasia With Female Fertility Angelika J. Dawson,1,2,3* Sandra Marles,2,3 Michelle Tomiuk,1 Diane Riordan,1 and Richard A. Gatti4 1
Cytogenetic Laboratory/HSC, Diagnostic Services of Manitoba, Winnipeg, Manitoba, Canada
2
Deptartments of Biochemistry & Medical Genetics and Pediatrics & Child Health, University of Manitoba, Winnipeg, Manitoba, Canada Genetics & Metabolism Program, WRHA, Winnipeg, Manitoba, Canada
3 4
Department of Pathology & Laboratory Medicine, and Human Genetics, UCLA/Geffen School of Medicine, Los Angeles, California
Manuscript Received: 23 December 2014; Manuscript Accepted: 15 March 2015
TO THE EDITOR Ataxia-telangiectasia (A-T) is an autosomal recessive chromosome instability syndrome characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, hyper-sensitivity to ionizing radiation, and cancer predisposition. Individuals with “classic” A-T are usually ataxic by age 2 years, and are often wheelchair-bound by age 10 years. Telangiectasias are typically evident by age 6 to10 years [Gatti, 2001; Chun and Gatti, 2004]. Milder phenotypes or atypical presentations of A-T have also been described in the literature [Chun and Gatti, 2004]. Some individuals with A-T have no neurological signs or symptoms [Trimis et al., 2004]. Others have no telangiectasias, even in adulthood [Chun and Gatti, 2004]. Mild ataxia, the onset of ataxia in adulthood, slow neurological deterioration, a progressive axonal sensorimotor polyneuropathy, and late-onset spinal muscular atrophy have also been described [Doerk et al., 2004; Verhagen et al., 2007; Byrd et al., 2013]. Extrapyramidal features are more prominent in older children. Dystonia or chorea may be the initial or most prominent manifestation of A-T. Oculomotor apraxia, drooling, progressive hypomimia, slow speech with abnormalities of articulation, and progressive difficulty with chewing and swallowing are commonly seen [Gatti, 2001]. Milder A-T phenotypes are thought to be associated with missense mutations and/or reduced (but more than trace) amounts of ATM (ataxia telangiectasia mutated) protein [Chun and Gatti, 2004], but exceptions do exist [Alterman et al., 2007; Mitui et al., 2009]. Serum alpha-fetoprotein (AFP) is a simple, rapid, and reliable screening test for A-T; it is elevated in more than 95% of A-T cases [Chun and Gatti, 2004]. Cytogenetic studies reveal rearrangement of chromosomes 7 and 14 in five to fifteen percent of normal peripheral blood lymphocytes in individuals with A-T [Lowery et al., 1994]. However, karyotyping may be technically difficult because the patients are often lymphopenic and the lymphocytes may not respond well to PHA. Confirmatory tests for A-T include the colony radiosensitivity assay (CSA) [Sun et al., 2002] and identification of the ATM protein by immunoblotting [Perlman et al., 2003; Chun and Gatti, 2004]. DNA sequencing is usually not definitive because the full spectrum of ATM mutations has not yet been established and not all mutations are detected by any single laboratory platform [Mitui et al., 2004].
Ó 2015 Wiley Periodicals, Inc.
How to Cite this Article: Dawson AJ, Marles S, Tomiuk M, Riordan D, Gatti RA. 2015. Ataxia-Telangiectasia with Female Fertility. Am J Med Genet Part A 9999A:1–3.
Prenatal diagnosis for A-T by direct mutation analysis of fetal DNA from amniocytes has been reported [Mancebo et al., 2007], as has preimplantation genetic diagnosis (PGD) for A-T [Hellani et al., 2002]. Early identification of A-T is now also accomplished by prenatal screening of Guthrie blood spots using the TREC (T-cell receptor excision circles) assay for detecting low levels of mature lymphocytes [Mallot et al., 2013]. Although infertility has been described as a major feature of A-T, there have been two reports of fertile A-T female patients with mild neurological phenotypes and null [Worth et al., 2013] and missense [Stankovic et al., 1998] mutations. Further, it should be noted that ATM -/- male and female knockout mice are infertile [Bhuller and Wells, 2006]. In this study, we report the clinical, cytogenetic, and molecular studies for two fertile females with previously undiagnosed ataxiatelangiectasia. Both carried the c.6200C>A mutation previously reported in Mennonite patients [Sandoval et al., 1999; Yanofsky et al., 2009; Saunders-Pullman et al., 2012; Nakamura et al., 2013]. Patient 1 was a 20-year-old Gravida 1 Para 0 Caucasian woman of Mennonite background referred to Genetics at 18 weeks gestation because of an elevated maternal serum AFP level of 6.07 MoM (normal range: A (A2067D) missense mutation carried on this haplotype [Nakamura et al., 2013]. The patient gave birth to an apparently normal, healthy boy at 41 weeks gestation with a birth weight of 3458.6 g. At 5 years 5 months of age, the boy was normally grown and had close to age appropriate development. He had no neurological symptoms, specifically no ataxia or gait disturbance, and his serum AFP was normal. This patient had two more pregnancies and had elevated levels of AFP in both (6.78 MoM and 7.74 MoM, respectively) (normal range A mutation was reported in one of 66 AT families diagnosed in Germany: p. Ala2067Asp(c.6200C>A)/p.Arg2227Cys (c.6679C>T) [Sandoval et al., 1999]. The c.6200C>A (Ala2067Asp) mutation was not found on >350 German non-AT chromosomes (personal communication, T. Doerk: Institute of Human Genetics, Medical School Hannover, D-30625 Hannover, Germany). The c.6200C>A mutation was traced to a grandparent from an Eastern Frisia village in northern Germany, near the Dutch border. This village is geographically quite close to Witmarsum in Western Frisia (the Dutch region of Frisia), where Menno Simons, an Anabaptist religious leader, lived and founded the Mennonite religion [Neff, 1957]. The c.6200C>A mutation appears to be a founder mutation in the Manitoba Mennonite population [Sandoval et al., 1999; Yanofsky et al., 2009; Nakamura et al., 2013]. The c.6200C>A mutation also appears to be associated with atypical A-T and an early-onset dystonia. It is a strong predictor for cancer susceptibility and adverse reactions to radiation or chemotherapy [Yanofsky et al., 2009; Saunders-Pullman et al., 2012; Nakamura et al., 2013]. As the c.6200c>A mutation is also associated with fertility, this suggests that even pregnant Mennonite women should be considered for A-T screening to identify them as early as possible so that appropriate oncological and neurological support can be instituted.
REFERENCES Alterman N, Fattal-Valevski A, Moyal L, Crawford TO, Lederman HM, Ziv Y, Shiloh Y. 2007. Ataxia-telangiectasia: Mild neurological presentation despite null ATM mutation and severe cellular phenotype. Am J Med Genet 43:1827–1834. Bhuller Y, Wells PG. 2006. A developmental role for ataxia-telangiectasia mutated in protecting the embryo from spontaneous and phenytoinenhanced embryopathies in culture. Toxicol Sci 93:156–163. Byrd PJ, Srinivasan V, Last JI, Smith A, Biggs P, Carney EF, Exley A, Abson C, Stewart GS, Izatt L, Taylor AM. 2012. Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia. Brit J Cancer 106:262–268. Chun HH, Gatti RA. 2004. Ataxia telangiectasia, an evolving phenotype. DNA Repair 3:1187–1196. Doerk T, Bendix-Waltes R, Wegner R-D, Stumm M. 2004. Slow progression of ataxia-telangiectasia with double missense and in frame splice mutations. Am J Hum Genet Part A 126A:272–277. Gatti RA. 2001. Ataxia-telangiectasia. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic & Molecular Bases of Inherited Disease 8th ed. pp. 705–721. New York, NY: McGraw-Hill. Hellani A, Lauge A, Ozand P, Jaroudi K, Coskun S. 2002. Pregnancy after preimplantation genetic diagnosis for Ataxia Telangiectasia. Mol Hum Reprod 8:785–788. Lowery MC, Sinclair-Hess C, Carey JC, Brothman AR. 1994. Ataxia telangiectasia revitalized: The importance of cytogenetic analysis in the diagnosis of A-T. Appl Cytogenet 20:49–51.
DAWSON ET AL. Mallott J, Kwan A, Church J, Gonzalez-Espinosa D, Tang LF, Sunderam U, Rana C, Srinivasan R, Brenner SE, Puck J. 2013. Newborn screening for SCID identifies patients with ataxia telangiectasia. J Clin Immunol 33:540–549. Mancebo E, Bernardo I, Castro MJ, Fernandez-Martinez FJ, Barreiro E, De-Pablos P, Marin MJ, Cortezon S, Paz-Artal E, Allende LM. 2007. Rapid molecular prenatal diagnosis of ataxia-telangiectasia by direct mutational analysis. Prenatal Diag 27:861–864. Mitui M, Nahas SA, Chun HH, Gatti RA. 2004. Diagnosis of ataxiatelangiectasia: ATM mutations associated with cancer. pp. 473-487. In Nakamura RM, Grody WW, Wu JT, Nagle RB, eds. Cancer Diagnostics: Current and Future Trends. Totowa, NJ: Humana Press. Nakamura K, Fike F, Haghahegh S, Saunders-Pullman R, Dawson A, Doerk T, Gatti RA. 2014. A-T Winnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity. Mol Genet & Genomic Med 2:332–340. Neff, Christian. 1957. Menno Simons Kerkje (Witmarsum, Friesland, Netherlands). Global Anabaptist Mennonite Encyclopedia Online. Retrieved 19 December 2014, from http://gameo.org/index.php?title=Menno_Simons_Kerkje_ (Witmarsum,_Friesland,_Netherlands)&oldid=104650. Perlman S, Becker-Catania S, Gatti RA. 2003. Ataxia-Telangiectasia: Diagnosis and Treatment. Semin Pediatr Neurol 10:173–182. Sandoval N, Platzer M, Rosenthal A, D€ oerk T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D. 1999. Characterization of ATM gene mutations in 66 ataxia telangiectasia families. Hum Mol Genet 8:69–79.
3 Saunders-Pullman R, Raymond D, Stoessl AJ, Hobson D, Nakamura K, Pullman S, Lefton D, Okun MS, Uitti R, Sachdev R, Stanley K, San Luciano M, Hagenah J, Gatti RA, Ozelius LJ, Bressman SB. 2012. Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites. Neurology 78:649–657. Stankovic T, Kidd AMJ, Sutcliffe A, McGuire GM, Robinson P, Weber P, Bedenham T, Bradwell AR, Easton DF, Lennox GG, Haites N, Byrd PJ, and Talyor AMR. 1998. ATM mutations and phenotypes in ataxia-telangiectasia familiees in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. Am J Hum Genet 62:334–345. Sun X, Becker-Catania SG, Chun HH, Hwang MJ, Huo Y, Wang Z, Mitui M, Sanal O, Chessa L, Crandall B, Gatti RA. 2002. Early diagnosis of ataxia-telangiectasia using radiosensitivity testing. J Pediatr 140: 724–731. Trimis GG, Athanassaki CK, Kanariou MM, Giannoulia-Karantana AA. 2004. Unusual absence of neurologic symptoms in a six-year old girl with ataxia-telangiectasia. J Postgrad Med 50:270–271. Verhagen MM, van Alfen N, Pillen S, Weemaes CM, Yntema JL, Hiel JA, Ter Laak H, van Deuren M, Broeks A, Willemsen MA. 2007. Neuromuscular abnormalities in ataxia telangiectasia: A clinical, electrophysiological, and muscle ultrasound study. Neuropediatrics 38:117–121. Worth PF, Srinivasan V, Smith A, Last JI, Wootton LL, Biggs PM, Davies NP, Carney EF, Byrd PJ, Taylor AM. 2013. Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia. Mov Disord 28:524–528. Yanofsky RA, Seshia SS, Dawson AJ, Stobart K, Greenberg CR, Booth FA, Prasad C, Del Bigio MR, Wrogemann JJ, Fike F, Gatti RA. 2009. Ataxiatelangiectasia: Atypical presentation and toxicity of cancer treatment. J Pediatr 36:462–467.
Ataxia-Telangiectasia With Female Fertility Angelika J. Dawson,1,2,3* Sandra Marles,2,3 Michelle Tomiuk,1 Diane Riordan,1 and Richard A. Gatti4 1
Cytogenetic Laboratory/HSC, Diagnostic Services of Manitoba, Winnipeg, Manitoba, Canada
2
Deptartments of Biochemistry & Medical Genetics and Pediatrics & Child Health, University of Manitoba, Winnipeg, Manitoba, Canada Genetics & Metabolism Program, WRHA, Winnipeg, Manitoba, Canada
3 4
Department of Pathology & Laboratory Medicine, and Human Genetics, UCLA/Geffen School of Medicine, Los Angeles, California
Manuscript Received: 23 December 2014; Manuscript Accepted: 15 March 2015
TO THE EDITOR Ataxia-telangiectasia (A-T) is an autosomal recessive chromosome instability syndrome characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, hyper-sensitivity to ionizing radiation, and cancer predisposition. Individuals with “classic” A-T are usually ataxic by age 2 years, and are often wheelchair-bound by age 10 years. Telangiectasias are typically evident by age 6 to10 years [Gatti, 2001; Chun and Gatti, 2004]. Milder phenotypes or atypical presentations of A-T have also been described in the literature [Chun and Gatti, 2004]. Some individuals with A-T have no neurological signs or symptoms [Trimis et al., 2004]. Others have no telangiectasias, even in adulthood [Chun and Gatti, 2004]. Mild ataxia, the onset of ataxia in adulthood, slow neurological deterioration, a progressive axonal sensorimotor polyneuropathy, and late-onset spinal muscular atrophy have also been described [Doerk et al., 2004; Verhagen et al., 2007; Byrd et al., 2013]. Extrapyramidal features are more prominent in older children. Dystonia or chorea may be the initial or most prominent manifestation of A-T. Oculomotor apraxia, drooling, progressive hypomimia, slow speech with abnormalities of articulation, and progressive difficulty with chewing and swallowing are commonly seen [Gatti, 2001]. Milder A-T phenotypes are thought to be associated with missense mutations and/or reduced (but more than trace) amounts of ATM (ataxia telangiectasia mutated) protein [Chun and Gatti, 2004], but exceptions do exist [Alterman et al., 2007; Mitui et al., 2009]. Serum alpha-fetoprotein (AFP) is a simple, rapid, and reliable screening test for A-T; it is elevated in more than 95% of A-T cases [Chun and Gatti, 2004]. Cytogenetic studies reveal rearrangement of chromosomes 7 and 14 in five to fifteen percent of normal peripheral blood lymphocytes in individuals with A-T [Lowery et al., 1994]. However, karyotyping may be technically difficult because the patients are often lymphopenic and the lymphocytes may not respond well to PHA. Confirmatory tests for A-T include the colony radiosensitivity assay (CSA) [Sun et al., 2002] and identification of the ATM protein by immunoblotting [Perlman et al., 2003; Chun and Gatti, 2004]. DNA sequencing is usually not definitive because the full spectrum of ATM mutations has not yet been established and not all mutations are detected by any single laboratory platform [Mitui et al., 2004].
Ó 2015 Wiley Periodicals, Inc.
How to Cite this Article: Dawson AJ, Marles S, Tomiuk M, Riordan D, Gatti RA. 2015. Ataxia-Telangiectasia with Female Fertility. Am J Med Genet Part A 9999A:1–3.
Prenatal diagnosis for A-T by direct mutation analysis of fetal DNA from amniocytes has been reported [Mancebo et al., 2007], as has preimplantation genetic diagnosis (PGD) for A-T [Hellani et al., 2002]. Early identification of A-T is now also accomplished by prenatal screening of Guthrie blood spots using the TREC (T-cell receptor excision circles) assay for detecting low levels of mature lymphocytes [Mallot et al., 2013]. Although infertility has been described as a major feature of A-T, there have been two reports of fertile A-T female patients with mild neurological phenotypes and null [Worth et al., 2013] and missense [Stankovic et al., 1998] mutations. Further, it should be noted that ATM -/- male and female knockout mice are infertile [Bhuller and Wells, 2006]. In this study, we report the clinical, cytogenetic, and molecular studies for two fertile females with previously undiagnosed ataxiatelangiectasia. Both carried the c.6200C>A mutation previously reported in Mennonite patients [Sandoval et al., 1999; Yanofsky et al., 2009; Saunders-Pullman et al., 2012; Nakamura et al., 2013]. Patient 1 was a 20-year-old Gravida 1 Para 0 Caucasian woman of Mennonite background referred to Genetics at 18 weeks gestation because of an elevated maternal serum AFP level of 6.07 MoM (normal range: A (A2067D) missense mutation carried on this haplotype [Nakamura et al., 2013]. The patient gave birth to an apparently normal, healthy boy at 41 weeks gestation with a birth weight of 3458.6 g. At 5 years 5 months of age, the boy was normally grown and had close to age appropriate development. He had no neurological symptoms, specifically no ataxia or gait disturbance, and his serum AFP was normal. This patient had two more pregnancies and had elevated levels of AFP in both (6.78 MoM and 7.74 MoM, respectively) (normal range A mutation was reported in one of 66 AT families diagnosed in Germany: p. Ala2067Asp(c.6200C>A)/p.Arg2227Cys (c.6679C>T) [Sandoval et al., 1999]. The c.6200C>A (Ala2067Asp) mutation was not found on >350 German non-AT chromosomes (personal communication, T. Doerk: Institute of Human Genetics, Medical School Hannover, D-30625 Hannover, Germany). The c.6200C>A mutation was traced to a grandparent from an Eastern Frisia village in northern Germany, near the Dutch border. This village is geographically quite close to Witmarsum in Western Frisia (the Dutch region of Frisia), where Menno Simons, an Anabaptist religious leader, lived and founded the Mennonite religion [Neff, 1957]. The c.6200C>A mutation appears to be a founder mutation in the Manitoba Mennonite population [Sandoval et al., 1999; Yanofsky et al., 2009; Nakamura et al., 2013]. The c.6200C>A mutation also appears to be associated with atypical A-T and an early-onset dystonia. It is a strong predictor for cancer susceptibility and adverse reactions to radiation or chemotherapy [Yanofsky et al., 2009; Saunders-Pullman et al., 2012; Nakamura et al., 2013]. As the c.6200c>A mutation is also associated with fertility, this suggests that even pregnant Mennonite women should be considered for A-T screening to identify them as early as possible so that appropriate oncological and neurological support can be instituted.
REFERENCES Alterman N, Fattal-Valevski A, Moyal L, Crawford TO, Lederman HM, Ziv Y, Shiloh Y. 2007. Ataxia-telangiectasia: Mild neurological presentation despite null ATM mutation and severe cellular phenotype. Am J Med Genet 43:1827–1834. Bhuller Y, Wells PG. 2006. A developmental role for ataxia-telangiectasia mutated in protecting the embryo from spontaneous and phenytoinenhanced embryopathies in culture. Toxicol Sci 93:156–163. Byrd PJ, Srinivasan V, Last JI, Smith A, Biggs P, Carney EF, Exley A, Abson C, Stewart GS, Izatt L, Taylor AM. 2012. Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia. Brit J Cancer 106:262–268. Chun HH, Gatti RA. 2004. Ataxia telangiectasia, an evolving phenotype. DNA Repair 3:1187–1196. Doerk T, Bendix-Waltes R, Wegner R-D, Stumm M. 2004. Slow progression of ataxia-telangiectasia with double missense and in frame splice mutations. Am J Hum Genet Part A 126A:272–277. Gatti RA. 2001. Ataxia-telangiectasia. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic & Molecular Bases of Inherited Disease 8th ed. pp. 705–721. New York, NY: McGraw-Hill. Hellani A, Lauge A, Ozand P, Jaroudi K, Coskun S. 2002. Pregnancy after preimplantation genetic diagnosis for Ataxia Telangiectasia. Mol Hum Reprod 8:785–788. Lowery MC, Sinclair-Hess C, Carey JC, Brothman AR. 1994. Ataxia telangiectasia revitalized: The importance of cytogenetic analysis in the diagnosis of A-T. Appl Cytogenet 20:49–51.
DAWSON ET AL. Mallott J, Kwan A, Church J, Gonzalez-Espinosa D, Tang LF, Sunderam U, Rana C, Srinivasan R, Brenner SE, Puck J. 2013. Newborn screening for SCID identifies patients with ataxia telangiectasia. J Clin Immunol 33:540–549. Mancebo E, Bernardo I, Castro MJ, Fernandez-Martinez FJ, Barreiro E, De-Pablos P, Marin MJ, Cortezon S, Paz-Artal E, Allende LM. 2007. Rapid molecular prenatal diagnosis of ataxia-telangiectasia by direct mutational analysis. Prenatal Diag 27:861–864. Mitui M, Nahas SA, Chun HH, Gatti RA. 2004. Diagnosis of ataxiatelangiectasia: ATM mutations associated with cancer. pp. 473-487. In Nakamura RM, Grody WW, Wu JT, Nagle RB, eds. Cancer Diagnostics: Current and Future Trends. Totowa, NJ: Humana Press. Nakamura K, Fike F, Haghahegh S, Saunders-Pullman R, Dawson A, Doerk T, Gatti RA. 2014. A-T Winnipeg: Pathogenesis of rare ATM missense mutation c.6200C>A with decreased protein expression and downstream signaling, early-onset dystonia, cancer, and life-threatening radiotoxicity. Mol Genet & Genomic Med 2:332–340. Neff, Christian. 1957. Menno Simons Kerkje (Witmarsum, Friesland, Netherlands). Global Anabaptist Mennonite Encyclopedia Online. Retrieved 19 December 2014, from http://gameo.org/index.php?title=Menno_Simons_Kerkje_ (Witmarsum,_Friesland,_Netherlands)&oldid=104650. Perlman S, Becker-Catania S, Gatti RA. 2003. Ataxia-Telangiectasia: Diagnosis and Treatment. Semin Pediatr Neurol 10:173–182. Sandoval N, Platzer M, Rosenthal A, D€ oerk T, Bendix R, Skawran B, Stuhrmann M, Wegner RD, Sperling K, Banin S, Shiloh Y, Baumer A, Bernthaler U, Sennefelder H, Brohm M, Weber BH, Schindler D. 1999. Characterization of ATM gene mutations in 66 ataxia telangiectasia families. Hum Mol Genet 8:69–79.
3 Saunders-Pullman R, Raymond D, Stoessl AJ, Hobson D, Nakamura K, Pullman S, Lefton D, Okun MS, Uitti R, Sachdev R, Stanley K, San Luciano M, Hagenah J, Gatti RA, Ozelius LJ, Bressman SB. 2012. Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites. Neurology 78:649–657. Stankovic T, Kidd AMJ, Sutcliffe A, McGuire GM, Robinson P, Weber P, Bedenham T, Bradwell AR, Easton DF, Lennox GG, Haites N, Byrd PJ, and Talyor AMR. 1998. ATM mutations and phenotypes in ataxia-telangiectasia familiees in the British Isles: expression of mutant ATM and the risk of leukemia, lymphoma, and breast cancer. Am J Hum Genet 62:334–345. Sun X, Becker-Catania SG, Chun HH, Hwang MJ, Huo Y, Wang Z, Mitui M, Sanal O, Chessa L, Crandall B, Gatti RA. 2002. Early diagnosis of ataxia-telangiectasia using radiosensitivity testing. J Pediatr 140: 724–731. Trimis GG, Athanassaki CK, Kanariou MM, Giannoulia-Karantana AA. 2004. Unusual absence of neurologic symptoms in a six-year old girl with ataxia-telangiectasia. J Postgrad Med 50:270–271. Verhagen MM, van Alfen N, Pillen S, Weemaes CM, Yntema JL, Hiel JA, Ter Laak H, van Deuren M, Broeks A, Willemsen MA. 2007. Neuromuscular abnormalities in ataxia telangiectasia: A clinical, electrophysiological, and muscle ultrasound study. Neuropediatrics 38:117–121. Worth PF, Srinivasan V, Smith A, Last JI, Wootton LL, Biggs PM, Davies NP, Carney EF, Byrd PJ, Taylor AM. 2013. Very mild presentation in adult with classical cellular phenotype of ataxia telangiectasia. Mov Disord 28:524–528. Yanofsky RA, Seshia SS, Dawson AJ, Stobart K, Greenberg CR, Booth FA, Prasad C, Del Bigio MR, Wrogemann JJ, Fike F, Gatti RA. 2009. Ataxiatelangiectasia: Atypical presentation and toxicity of cancer treatment. J Pediatr 36:462–467.
