Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations

Sandra Mercier (Lead / Corresponding author), Sébastien Küry, Emmanuelle Salort-Campana, Armelle Magot, Uchenna Agbim, Thomas Besnard, Nathalie Bodak, Chantal Bou-Hanna, Flora Bréhéret, Perrine Brunelle, Florence Caillon, Brigitte Chabrol, Valérie Cormier-Daire, Albert David, Bruno Eymard, Laurence Faivre, Dominique Figarella-Branger, Emmanuelle Fleurence, Mythily Ganapathi, Romain Gherardi & 34 others Alice Goldenberg, Antoine Hamel, Jeanine Igual, Alan D. Irvine, Dominique Israël-Biet, Caroline Kannengiesser, Christian Laboisse, Cédric Le Caignec, Jean Yves Mahé, Stéphanie Mallet, Stuart MacGowan, Maeve A. McAleer, Irwin McLean, Cécile Méni, Arnold Munnich, Jean Marie Mussini, Peter L. Nagy, Jeffrey Odel, Grainne M. O'Regan, Yann Péréon, Julie Perrier, Juliette Piard, Eve Puzenat, Jacinda B. Sampson, Frances Smith, Nadem Soufir, Kurenai Tanji, Christel Thauvin, Christina Ulane, Rosemarie M. Watson, Nonhlanhla P. Khumalo, Bongani M. Mayosi, Sébastien Barbarot, Stéphane Bézieau

Research output: Contribution to journalArticle

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Abstract

Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM-198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. Conclusions: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.

Original languageEnglish
Article number135
Number of pages16
JournalOrphanet Journal of Rare Diseases
Volume10
DOIs
Publication statusPublished - 15 Oct 2015

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Pulmonary Fibrosis
Contracture
Muscular Diseases
Tendons
Mutation
Hypotrichosis
Hypohidrosis
Exome
Exocrine Pancreatic Insufficiency
Muscles
Muscular Atrophy
Muscle Weakness
Pathologic Processes
Trypsin
Serine
Genes
Cysteine
Microscopy
Skeletal Muscle
Fibrosis

Keywords

  • Adiposis
  • Contractures
  • Myopathy
  • Poikiloderma
  • Pulmonary fibrosis

Cite this

Mercier, Sandra ; Küry, Sébastien ; Salort-Campana, Emmanuelle ; Magot, Armelle ; Agbim, Uchenna ; Besnard, Thomas ; Bodak, Nathalie ; Bou-Hanna, Chantal ; Bréhéret, Flora ; Brunelle, Perrine ; Caillon, Florence ; Chabrol, Brigitte ; Cormier-Daire, Valérie ; David, Albert ; Eymard, Bruno ; Faivre, Laurence ; Figarella-Branger, Dominique ; Fleurence, Emmanuelle ; Ganapathi, Mythily ; Gherardi, Romain ; Goldenberg, Alice ; Hamel, Antoine ; Igual, Jeanine ; Irvine, Alan D. ; Israël-Biet, Dominique ; Kannengiesser, Caroline ; Laboisse, Christian ; Le Caignec, Cédric ; Mahé, Jean Yves ; Mallet, Stéphanie ; MacGowan, Stuart ; McAleer, Maeve A. ; McLean, Irwin ; Méni, Cécile ; Munnich, Arnold ; Mussini, Jean Marie ; Nagy, Peter L. ; Odel, Jeffrey ; O'Regan, Grainne M. ; Péréon, Yann ; Perrier, Julie ; Piard, Juliette ; Puzenat, Eve ; Sampson, Jacinda B. ; Smith, Frances ; Soufir, Nadem ; Tanji, Kurenai ; Thauvin, Christel ; Ulane, Christina ; Watson, Rosemarie M. ; Khumalo, Nonhlanhla P. ; Mayosi, Bongani M. ; Barbarot, Sébastien ; Bézieau, Stéphane. / Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations. In: Orphanet Journal of Rare Diseases. 2015 ; Vol. 10.
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title = "Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations",
abstract = "Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM-198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. Conclusions: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.",
keywords = "Adiposis, Contractures, Myopathy, Poikiloderma, Pulmonary fibrosis",
author = "Sandra Mercier and S{\'e}bastien K{\"u}ry and Emmanuelle Salort-Campana and Armelle Magot and Uchenna Agbim and Thomas Besnard and Nathalie Bodak and Chantal Bou-Hanna and Flora Br{\'e}h{\'e}ret and Perrine Brunelle and Florence Caillon and Brigitte Chabrol and Val{\'e}rie Cormier-Daire and Albert David and Bruno Eymard and Laurence Faivre and Dominique Figarella-Branger and Emmanuelle Fleurence and Mythily Ganapathi and Romain Gherardi and Alice Goldenberg and Antoine Hamel and Jeanine Igual and Irvine, {Alan D.} and Dominique Isra{\"e}l-Biet and Caroline Kannengiesser and Christian Laboisse and {Le Caignec}, C{\'e}dric and Mah{\'e}, {Jean Yves} and St{\'e}phanie Mallet and Stuart MacGowan and McAleer, {Maeve A.} and Irwin McLean and C{\'e}cile M{\'e}ni and Arnold Munnich and Mussini, {Jean Marie} and Nagy, {Peter L.} and Jeffrey Odel and O'Regan, {Grainne M.} and Yann P{\'e}r{\'e}on and Julie Perrier and Juliette Piard and Eve Puzenat and Sampson, {Jacinda B.} and Frances Smith and Nadem Soufir and Kurenai Tanji and Christel Thauvin and Christina Ulane and Watson, {Rosemarie M.} and Khumalo, {Nonhlanhla P.} and Mayosi, {Bongani M.} and S{\'e}bastien Barbarot and St{\'e}phane B{\'e}zieau",
year = "2015",
month = "10",
day = "15",
doi = "10.1186/s13023-015-0352-4",
language = "English",
volume = "10",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
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Mercier, S, Küry, S, Salort-Campana, E, Magot, A, Agbim, U, Besnard, T, Bodak, N, Bou-Hanna, C, Bréhéret, F, Brunelle, P, Caillon, F, Chabrol, B, Cormier-Daire, V, David, A, Eymard, B, Faivre, L, Figarella-Branger, D, Fleurence, E, Ganapathi, M, Gherardi, R, Goldenberg, A, Hamel, A, Igual, J, Irvine, AD, Israël-Biet, D, Kannengiesser, C, Laboisse, C, Le Caignec, C, Mahé, JY, Mallet, S, MacGowan, S, McAleer, MA, McLean, I, Méni, C, Munnich, A, Mussini, JM, Nagy, PL, Odel, J, O'Regan, GM, Péréon, Y, Perrier, J, Piard, J, Puzenat, E, Sampson, JB, Smith, F, Soufir, N, Tanji, K, Thauvin, C, Ulane, C, Watson, RM, Khumalo, NP, Mayosi, BM, Barbarot, S & Bézieau, S 2015, 'Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations', Orphanet Journal of Rare Diseases, vol. 10, 135. https://doi.org/10.1186/s13023-015-0352-4

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations. / Mercier, Sandra (Lead / Corresponding author); Küry, Sébastien; Salort-Campana, Emmanuelle; Magot, Armelle; Agbim, Uchenna; Besnard, Thomas; Bodak, Nathalie; Bou-Hanna, Chantal; Bréhéret, Flora; Brunelle, Perrine; Caillon, Florence; Chabrol, Brigitte; Cormier-Daire, Valérie; David, Albert; Eymard, Bruno; Faivre, Laurence; Figarella-Branger, Dominique; Fleurence, Emmanuelle; Ganapathi, Mythily; Gherardi, Romain; Goldenberg, Alice; Hamel, Antoine; Igual, Jeanine; Irvine, Alan D.; Israël-Biet, Dominique; Kannengiesser, Caroline; Laboisse, Christian; Le Caignec, Cédric; Mahé, Jean Yves; Mallet, Stéphanie; MacGowan, Stuart; McAleer, Maeve A.; McLean, Irwin; Méni, Cécile; Munnich, Arnold; Mussini, Jean Marie; Nagy, Peter L.; Odel, Jeffrey; O'Regan, Grainne M.; Péréon, Yann; Perrier, Julie; Piard, Juliette; Puzenat, Eve; Sampson, Jacinda B.; Smith, Frances; Soufir, Nadem; Tanji, Kurenai; Thauvin, Christel; Ulane, Christina; Watson, Rosemarie M.; Khumalo, Nonhlanhla P.; Mayosi, Bongani M.; Barbarot, Sébastien; Bézieau, Stéphane.

In: Orphanet Journal of Rare Diseases, Vol. 10, 135, 15.10.2015.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to FAM111B mutations

AU - Mercier, Sandra

AU - Küry, Sébastien

AU - Salort-Campana, Emmanuelle

AU - Magot, Armelle

AU - Agbim, Uchenna

AU - Besnard, Thomas

AU - Bodak, Nathalie

AU - Bou-Hanna, Chantal

AU - Bréhéret, Flora

AU - Brunelle, Perrine

AU - Caillon, Florence

AU - Chabrol, Brigitte

AU - Cormier-Daire, Valérie

AU - David, Albert

AU - Eymard, Bruno

AU - Faivre, Laurence

AU - Figarella-Branger, Dominique

AU - Fleurence, Emmanuelle

AU - Ganapathi, Mythily

AU - Gherardi, Romain

AU - Goldenberg, Alice

AU - Hamel, Antoine

AU - Igual, Jeanine

AU - Irvine, Alan D.

AU - Israël-Biet, Dominique

AU - Kannengiesser, Caroline

AU - Laboisse, Christian

AU - Le Caignec, Cédric

AU - Mahé, Jean Yves

AU - Mallet, Stéphanie

AU - MacGowan, Stuart

AU - McAleer, Maeve A.

AU - McLean, Irwin

AU - Méni, Cécile

AU - Munnich, Arnold

AU - Mussini, Jean Marie

AU - Nagy, Peter L.

AU - Odel, Jeffrey

AU - O'Regan, Grainne M.

AU - Péréon, Yann

AU - Perrier, Julie

AU - Piard, Juliette

AU - Puzenat, Eve

AU - Sampson, Jacinda B.

AU - Smith, Frances

AU - Soufir, Nadem

AU - Tanji, Kurenai

AU - Thauvin, Christel

AU - Ulane, Christina

AU - Watson, Rosemarie M.

AU - Khumalo, Nonhlanhla P.

AU - Mayosi, Bongani M.

AU - Barbarot, Sébastien

AU - Bézieau, Stéphane

PY - 2015/10/15

Y1 - 2015/10/15

N2 - Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM-198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. Conclusions: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.

AB - Background: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM-198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. Methods: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. Results: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. Conclusions: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder.

KW - Adiposis

KW - Contractures

KW - Myopathy

KW - Poikiloderma

KW - Pulmonary fibrosis

UR - http://www.scopus.com/inward/record.url?scp=84945200813&partnerID=8YFLogxK

U2 - 10.1186/s13023-015-0352-4

DO - 10.1186/s13023-015-0352-4

M3 - Article

VL - 10

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

M1 - 135

ER -