First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome: a case report

Anwar Baban, Monia Magliozzi, Bart Loeys, Rachele Adorisio, Viola Alesi, Aurelio Secinaro, Bernadette Corica, Luca Vricella, Harry C Dietz, Fabrizio Drago, Antonio Novelli, Antonio Amodeo

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.

CASE PRESENTATION: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far.

CONCLUSIONS: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.

Original languageEnglish
Pages (from-to)170
JournalBMC Medical Genetics
Volume19
Issue number1
DOIs
Publication statusPublished - Sep 15 2018

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Loeys-Dietz Syndrome
Mosaicism
Mutation
Cheek
Iris
Hair
Dilatation
Oculocutaneous Albinism
Mothers
Uvula
Inborn Genetic Diseases
Retinal Pigments
Inguinal Hernia
Abdominal Aorta
Missense Mutation
Thoracic Aorta
Mitral Valve
Fathers
Blood Vessels
Leukocytes

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First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome : a case report. / Baban, Anwar; Magliozzi, Monia; Loeys, Bart; Adorisio, Rachele; Alesi, Viola; Secinaro, Aurelio; Corica, Bernadette; Vricella, Luca; Dietz, Harry C; Drago, Fabrizio; Novelli, Antonio; Amodeo, Antonio.

In: BMC Medical Genetics, Vol. 19, No. 1, 15.09.2018, p. 170.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.CASE PRESENTATION: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18{\%} in peripheral blood leukocytes, 18{\%} in buccal cells and 10{\%} in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far.CONCLUSIONS: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.",
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T1 - First evidence of maternally inherited mosaicism in TGFBR1 and subtle primary myocardial changes in Loeys-Dietz syndrome

T2 - a case report

AU - Baban, Anwar

AU - Magliozzi, Monia

AU - Loeys, Bart

AU - Adorisio, Rachele

AU - Alesi, Viola

AU - Secinaro, Aurelio

AU - Corica, Bernadette

AU - Vricella, Luca

AU - Dietz, Harry C

AU - Drago, Fabrizio

AU - Novelli, Antonio

AU - Amodeo, Antonio

PY - 2018/9/15

Y1 - 2018/9/15

N2 - BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.CASE PRESENTATION: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far.CONCLUSIONS: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.

AB - BACKGROUND: Loeys-Dietz syndrome (LDS) is a rare multisystemic disorder characterized by vascular and skeletal abnormalities, with considerable intra- and interfamilial variability.CASE PRESENTATION: We report the case of an 8-year-old male with clinical features of two distinct genetic disorders, namely LDS, manifesting in the first months by progressive aortic root dilatation, arterial tortuosity, bifid uvula, and inguinal hernias and oculocutaneous albinism (OCA) manifesting by white hair and skin that does not tan, nystagmus, reduced iris pigment with iris translucency, and reduced retinal pigment). We identified previously reported, homozygous mutations of TYR, c.1A > G (p.Met1Val) and heterozygous, missense mutation of TGFBR1, c.1460G > A (p.Arg487Gln). Family history revealed that his mother underwent multiple surgical repairs for recurrent hemorrhage originating from the buccal artery. Molecular studies confirmed a maternally inherited low grade TGFBR1 mutation somatic mosaicism (18% in peripheral blood leukocytes, 18% in buccal cells and 10% in hair root cells). Maternal cardiac investigations revealed peculiar cardiovascular features: mild tortuosity at the aortic arch, dilatation of the proximal abdominal aorta, multiple deep left ventricular myocardial crypts, and dysplastic mitral valve. TGFBR2 germline mosaicism has been described in three fathers of children carrying TGFBR2 mutations but, to the best of our knowledge, no case of maternally inherited TGFBR1 mutation mosaicism has been reported so far.CONCLUSIONS: This case report suggests that individuals with somatic mosaicism might be at risk for mild and unusual forms of LDS but germline mosaicism can lead to full blown picture of the disease in offspring.

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DO - 10.1186/s12881-018-0661-2

M3 - Article

C2 - 30219046

VL - 19

SP - 170

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

IS - 1

ER -